deliveroo interview case study

20 Deliveroo Interview Questions and Answers

Prepare for the types of questions you are likely to be asked when interviewing for a position at Deliveroo.

Deliveroo is a food delivery service that allows users to order restaurant meals using the web and mobile. The company was founded in 2013 and is headquartered in London, England. Deliveroo operates in over 200 cities in 12 countries.

If you’re interviewing for a job at Deliveroo, you can expect to be asked questions about your experience with customer service, your ability to work in a fast-paced environment, and your knowledge of the food delivery industry. You may also be asked questions about your ability to use technology, such as the Deliveroo app, to place orders and track deliveries.

Deliveroo Interview Process

The interview process at Deliveroo can vary depending on the position you are applying for. However, most positions will require at least one phone screen with a recruiter, followed by one or more in-person interviews. For some positions, like software engineering, there may also be a take-home coding assessment. Overall, the interview process is generally positive, but some candidates have found it to be excessively long or difficult.

• Why do you want to work as a rider?
• What is your availability like on weekdays and weekends?
• Do you have any experience working in the food industry?
• How would you handle an upset customer if their order was wrong?
• Tell me about a time when you were challenged by a problem you had to solve, how did you approach it?
• Describe some of your previous courier jobs.
• How would you describe your riding skills?
• Where do you see yourself in 5 years?
• How would you respond if a restaurant called you complaining that one of our riders stole from them?
• If a delivery took longer than usual, what would you tell the customer?
• Have you worked in an environment where you had to do multiple tasks at once?
• Describe your experience with sales.
• Which area of account management are you most interested in?
• How comfortable are you dealing with difficult customers?
• Are you able to meet all of the requirements for being an account manager?
• We need someone who is capable of having challenging conversations. Can you give us an example of a time when you had to be assertive?
• What do you think makes a good account manager?
• Do you have experience using Excel?
• What would you say is your greatest strength and weakness?
• Deliveroo wants to continuously improve its service. How would you help us achieve that goal?

1. Why do you want to work as a rider?

This question can help the interviewer get to know you better and understand why you’re interested in working for Deliveroo. Use your answer to share a few reasons why you want this job, what skills you have that make you qualified and how you plan to contribute to the company’s success.

Example: “I’ve always been passionate about food, so I’m excited to work as a rider with Deliveroo. I love meeting new people and learning about different cultures, so I think this job would be a great fit for me. I also enjoy being active and getting outside, which is another reason I’m excited to start delivering meals.”

2. What is your availability like on weekdays and weekends?

Employers ask this question to make sure you’re available for the hours they need. If you have a full-time job, let them know that you can work weekends and evenings. If you are looking for more than one job, explain that you can work any time of day or night.

Example: “I am available to work weekdays from 5 p.m. until 10 p.m., and I’m also available on weekends from noon until midnight. I am currently looking for another part-time job, so if your company is only open during certain times, I would be willing to adjust my schedule.”

3. Do you have any experience working in the food industry?

This question is an opportunity to share your experience with the interviewer. If you have previous food industry experience, be sure to highlight any transferable skills that will help you succeed in this role.

Example: “I worked as a server at a local restaurant for two years while I was in college. This job taught me how to multitask and manage many orders at once. It also helped me develop my communication skills and learn how to work well under pressure. These are all valuable skills that I can apply to this position.”

4. How would you handle an upset customer if their order was wrong?

An interviewer may ask this question to assess your customer service skills. They want to know that you can handle a variety of situations and respond with empathy and professionalism. In your answer, try to show how you would use your problem-solving skills to resolve the situation quickly.

Example: “I would first apologize for the mistake and then offer to remake their order at no charge. I would also give them a coupon code for free delivery on their next order as an apology. If they still wanted to speak to someone higher up, I would connect them to my manager or supervisor so they could explain the issue further.”

5. Tell me about a time when you were challenged by a problem you had to solve, how did you approach it?

This question is a great way to show your problem-solving skills and how you approach challenges. When answering this question, it can be helpful to describe the steps you took to solve the issue and what you learned from the experience.

Example: “When I was working as a server at a restaurant, we were short on staff one night and I had to cover two servers’ tables by myself. This caused me to get behind in my orders, which made some customers unhappy. I approached the situation by asking for help from other staff members so that I could focus on taking care of my own tables. After that, I worked hard to make sure all of my customers received their food quickly.”

6. Describe some of your previous courier jobs.

This question is a great way to learn more about your interviewers and their company culture. When answering this question, it can be helpful to mention any unique or interesting aspects of the courier job you’re applying for.

Example: “I’ve worked as a courier for several different companies in my career. I started out working for a small courier service that specialized in delivering food orders from local restaurants. This was an excellent opportunity for me to practice driving in busy areas and honing my customer service skills. After that, I moved on to work for a larger courier service where I learned how to manage multiple deliveries at once.”

7. How would you describe your riding skills?

This question is an opportunity to show your interviewer that you have the skills and experience necessary for this role. You can answer this question by describing your riding background, including any certifications or licenses you may have.

Example: “I’ve been riding a bike since I was a child, so I’m quite comfortable on two wheels. In fact, I took my state’s cycling test when I was 16 and passed with flying colors. I also completed a course in defensive cycling last year, which has helped me become more aware of my surroundings while riding.”

8. Where do you see yourself in 5 years?

This question is a common one in interviews, and it’s often asked to see if you have career goals. When answering this question, be honest about your future plans but also show that you’re willing to stay with the company for several years.

Example: “I plan on staying in my current field for at least five more years. I love working with people and helping them find great food, so I would like to continue doing that as long as possible. In five years, I hope to have moved up within the company and gained some valuable experience.”

9. How would you respond if a restaurant called you complaining that one of our riders stole from them?

This question is a great way to assess your customer service skills and how you would respond in an emergency situation.

Example: “If I received a call from a restaurant claiming that one of our riders stole something, I would first ask for the rider’s name so I could check their record. If they had no prior incidents, I would tell them that we would investigate the claim and take appropriate action if necessary. If the rider did have prior incidents, I would immediately terminate their contract with Deliveroo.”

10. If a delivery took longer than usual, what would you tell the customer?

This question can help interviewers assess your customer service skills. When answering, it can be helpful to mention a specific example of how you handled this situation in the past.

Example: “If a delivery took longer than usual, I would first apologize and explain why there was a delay. Then, I would offer a discount on their next order or free dessert. This shows customers that I care about their experience and want to make sure they come back.”

11. Have you worked in an environment where you had to do multiple tasks at once?

This question can help the interviewer understand how you handle multitasking and whether or not you have experience with it. If you do, share a specific example of when you had to multitask and what your results were.

Example: “In my previous position as a server at a restaurant, I was responsible for taking orders from customers while also delivering food to tables. This required me to multitask between talking to customers about their orders and checking on other tables to see if they needed anything. While this is different than working in an office environment, I am used to multitasking and feel confident that I could successfully perform multiple tasks at once.”

12. Describe your experience with sales.

This question is an opportunity to show your experience with a specific skill that’s important for the role. If you have sales experience, describe how it helped you in previous roles.

Example: “I’ve had several experiences with sales throughout my career. In my first job as a server at a restaurant, I learned about customer service and building relationships with customers. As I gained more experience, I became better at selling myself and my skills to customers. This led to me getting promoted to a lead server position where I was responsible for training new servers.”

13. Which area of account management are you most interested in?

This question is a great way to show your knowledge of the role and how you can contribute to the company. Account managers are responsible for managing clients, so it’s important that you’re passionate about this aspect of the job.

Example: “I’m most interested in client retention because I believe it’s crucial to keep customers happy. In my previous position, I developed a system where we could track customer satisfaction and use that information to improve our service. This led to an increase in sales by 10% over the course of six months.”

14. How comfortable are you dealing with difficult customers?

When working for a company that delivers food, you may encounter customers who are unhappy with their orders. Employers ask this question to make sure you have the skills necessary to handle these situations. In your answer, explain how you would approach this situation and what steps you would take to resolve it.

Example: “I understand that delivering food can be challenging at times. I am always prepared to help customers when they need assistance. If someone is upset about their order, I will listen to them carefully and try my best to resolve the issue. If there’s nothing I can do, I will apologize and offer them a discount on their next order.”

15. Are you able to meet all of the requirements for being an account manager?

Account managers are responsible for managing client relationships and ensuring that the company meets its clients’ needs. An interviewer may ask this question to determine if you have the skills necessary to succeed in this role. Before your interview, review the job description to identify what an account manager should be able to do. In your response, explain how your experience and skills match up with these requirements.

Example: “I believe I am well-suited to be an account manager at Deliveroo because of my strong communication skills. Throughout my career, I’ve worked as a customer service representative, which has given me valuable insight into what customers want from their interactions with businesses. I also understand the importance of meeting deadlines and can use my organizational skills to ensure that all deliverables are submitted on time.”

16. We need someone who is capable of having challenging conversations. Can you give us an example of a time when you had to be assertive?

This question is a great way to assess your communication skills and how you can handle conflict. When answering this question, it’s important to be honest about the situation and highlight what you learned from it.

Example: “I had an instance where I was working with a client who wanted me to complete a project by a certain deadline. However, I didn’t think that I could meet their expectations because of other projects I was already working on. Instead of avoiding the conversation, I spoke up and explained my reasoning for why I couldn’t finish the work in time. The client understood my position and gave me more time to complete the project.”

17. What do you think makes a good account manager?

Account managers are responsible for managing the relationships between clients and their company. They must be able to communicate effectively, solve problems and maintain a positive relationship with customers. Your answer should show that you understand what makes an effective account manager and can apply those skills to your own work.

Example: “I think a good account manager is someone who has excellent communication skills. Account managers need to be able to listen to customer concerns and respond in a way that helps them feel heard. I also think it’s important to have strong problem-solving skills because sometimes there may be issues with orders or delivery times. Being able to find solutions quickly can help keep customers happy.”

18. Do you have experience using Excel?

Excel is a popular spreadsheet program that many businesses use to organize data. If you have experience using Excel, the interviewer may ask you to describe how you used it in your previous job.

Example: “I’ve been using Excel for several years now and I find it an effective tool for organizing large amounts of data. In my last position, I was responsible for entering customer orders into our database each day. I would enter all of the information from customers’ receipts into Excel, including their names, addresses, phone numbers and meal choices. Then, I would sort the data by date or category so that I could easily access it when needed.”

19. What would you say is your greatest strength and weakness?

This question is a common one in interviews, and it’s important to be honest when answering. Employers want to know what your greatest strengths are so they can use them to help you succeed at the job. They also want to know about any weaknesses so they can help you improve or work around them.

Example: “My greatest strength is my ability to multitask. I am able to manage many tasks at once while still maintaining quality results. My weakness would be that sometimes I get overwhelmed with too much work. If this happens, I try to take a break and regroup before getting back to work.”

20. Deliveroo wants to continuously improve its service. How would you help us achieve that goal?

This question is an opportunity to show your problem-solving skills and ability to think creatively.

Example: “I would start by analyzing the current system, looking for areas that could be improved. I’d then create a plan of action with specific goals and deadlines. For example, if one goal was to reduce customer wait times, I might implement a new software program that allows customers to track their food delivery in real time. This way, they can see when their meal will arrive and not have to wait as long.”

20 Agility Interview Questions and Answers

20 docebo interview questions and answers, you may also be interested in..., 20 aws simple notification service interview questions and answers, 17 accounts payable team leader interview questions and answers, 17 assistant video editor interview questions and answers, 17 clinic supervisor interview questions and answers.

“It’s always harder to change ways of working when that’s the way things have always been done… But I cannot begin to tell you how much easier it is now that we’re used to using Weploy”

Tarrady Prowse

Customer Care Manager

Founded in 2013, Deliveroo is one of the world’s fastest growing online food delivery services. With a mission to transform the way customers eat, Deliveroo today partners with over 14,000 restaurants and 8,000 riders to deliver great food to Australians across 13 cities.

How deliveroo created efficiencies in their on and offshore customer service teams by using weploy....

Reduced 2 hours 20 minutes of rostering time, into 10 minutes per week

Standardised staff quality, every time

Scale up support in minutes for a team of 20 onshore reps

The Challenge...

Hiring quality talent for values fit at Deliveroo involves a comprehensive series of calls and face to face interviews, each carefully designed to uncover those who have the kind of respectful attitude that complement their number one Company Value: “ Customer Obsession ”.

Tarrady Prowse manages Customer Care for the APAC region. Her and her team manage thousands of inbound enquiries coming in around the clock, from an extensive network of riders and restaurants, as well as customers. Each enquiry must be sorted, responded to, and escalated if necessary. Tarrady needs a team of self-starters with excellent verbal and written skills, whom she can rely on to act autonomously with sensitivity and accuracy. 

Using a rostering platform to manage the scheduling of 20+ Customer Service team members was a complex game of moving parts. A sizeable percentage of the team being students with shifting class timetables, the rosters required changes week to week, day to day. Tarrady was juggling requests for shift swaps that would come through via text, emails and late night phone calls, spending a minimum of 20 minutes per day on this kind of admin.

The Solution...

“now, i spend max 10 minutes a week scheduling. timesheets are sent to me which i can approve with one click, saving me all those hours reconciling individual shifts with invoices”.

Head of People at Deliveroo Kirsty Seaborne came across Weploy and recommended Tarrady give it a try. She was pleased to find it was easy and intuitive to use without any training or onboarding. 

The Benefits...

By putting their trust in Weploy for their short-term hiring needs, Deliveroo is able to put their Customer Centricity into practise. Consistent, quality support means that the Customer Experience is always a positive one. Using the Weploy platform means that admin time spent on scheduling has been slashed and Tarrady can focus on the things she loves most about her job - strategy, training and people management. Given the importance of the right kind of talent internally at Deliveroo, it is comforting to know that hiring managers can review past jobs and choose from Weployees who have previously worked and gone through the required training already. This has meant that up to three different departments are now hiring via Weploy, each hiring manager having their own access to the company dashboard, and feedback from all stakeholders has been positive. 

Start valuing your time more...

• How it works
• What is a Weployee
• Book a demo

Get In Touch

Let us know about you and your company and we will be in touch to arrange a free global expansion consultation.

Why Centuro

Countries Covered

Individuals Relocated

Cross-border Experience

Interactive Platform

An international expansion case study: Deliveroo

This case study explores the deliveroo global expansion strategy, why it was successful, and how effective business planning turned them into a global household name., origins of deliveroo.

After making the move from New York to London, Co-Founder, and CEO Will Shu was astounded to realize that it was very difficult to get ready-made food delivered to consumers. As a result, he made it his personal mission to bring restaurants closer to their customers. This led to the launch of Deliveroo in February 2013. Before going global, Deliveroo started as a small company in the US with very few sales and minimal stock listings. In its 3rd year, revenue grew to £18 million and the company began to grow and develop significantly.

How much has Deliveroo grown?  

In 2021, Deliveroo won Best Beats First Category Company in the Real Innovation Awards. Moreover, it was crowned the fastest growing technology firm in the UK by Deloitte. Over the last 4 years, it has achieved an incredible growth rate of 107,117%. This year, the company is in the rankings again, proving that it has the momentum to maintain its steep growth trajectory.

Currently, the company is valued at US $2 billion (£1.5 billion), making it one of Britain’s most valuable private companies despite having recorded a gross profit of less than 1% in 2021. In addition, Deliveroo has raised over $900m since it was established, and this has given it the opportunity to expand in other countries. The company is growing at an extraordinary rate, partnering with thousands of popular restaurants to deliver great food to customers’ doorsteps.

What led to Deliveroo’s global expansion success?  

Without a doubt, Deliveroo is ahead of the competition since it heavily invests in resources that afford it a competitive advantage. To be precise, the crux of its success lies deeply in its prompt responses to customer demands and concerns, and this is made possible by its data-driven decision-making process.

The firm was also able to raise over $200 million (£132 million) last year, and this has partly contributed to its meteoric rise. Unlike its competition, Deliveroo has transformed the way consumers order food by making it possible for its customers to indulge in-home delivery from restaurants that were not making deliveries. Today, customers can get reliable and quick deliveries from more than 750 premium London hotels thanks to its massive network of 300 freelance drivers.

The efficiency and adeptness of the company can also be attributed to big data and machine learning. Dan Webb, the company’s VP of engineering, says that “ever since the company was established, the use of data has been pivotal to ensuring that riders, customers, and restaurants get the best possible experience.”

Deliveroo uses data in 3 key ways:

– To support team decisions . Constant experimentation has enabled the company to comprehend product changes. According to Webb, graphs and data help their operations teams to comprehend and react to trends.

– To provide support for recommendations and decisions . The company uses machine-learning models that need to be retrained to make sure that the company is making decisions and recommendations using relevant and up-to-date information.

– To provide ‘real-time operational monitoring . Since Deliveroo’s operations are mostly in busy cities, connecting customers to restaurants and riders is always unpredictable. To overcome this, the company uses real-time data to identify and react to challenges that may arise.

By leveraging on data, their dispatch engine, ‘Frank’ is able to continuously calculate and match the ideal combination of riders and restaurants with customer orders. These predictions and calculations are based on machine learning algorithms trained to identify and react to challenges that may arise.

How many countries does Deliveroo operate in?  

Deliveroo has transformed itself into a global company that operates in over 800 cities and towns across 12 markets. These include Hong Kong, Belgium, France, the United Arab Emirates, Italy, Ireland, the Netherlands, Singapore, the United Kingdom, Spain, Kuwait, and Australia.

How many employees does Deliveroo have?  

Deliveroo has partnered with more than 140,000 takeaways and restaurants. It also boasts over 110,000 riders that provide food delivery services across the globe. Moreover, it has over 2,000 employees in offices around the world.

Challenges Deliveroo faced  

Shifting customer preferences  

The main aim of Deliveroo was to grow its market share by offering the best possible deals to its customers at an affordable price. Unfortunately, players in the food delivery niche have elevated the marketing game to such a level that customers are spoilt for choice. This made it hard for the company to build brand loyalty.

Volatile Market Prices  

Apart from growing its customer base, the company has also decried the high volatility of food prices. The company says that it has been hard to track and keep up with market prices, and this has made it difficult to implement an ideal pricing strategy.

Observance of Food Quality Standards  

Due to a massive demand for orders, delivering food to customers who are far away from restaurants while maintaining quality has been a challenge for Deliveroo. The problem is that the food served in restaurants and the one being delivered to customers create a significant loophole that the company is striving to overcome.

Managing Customer Expectations   

Regardless of the success that Deliveroo has had, it has been finding it hard to satisfy customer demands. The company has publicly stated that customer satisfaction is not just a matter of their delivery partners but also those working at the point of origin. As a result, it has been a challenge for the company to fill the gap that exists between restaurant workers and delivery partners.

Despite the challenges faced by Deliveroo, it has established itself as a big wig in the food delivery industry. And though it is yet to make substantial profits, we should expect the company to continue its growth, largely due to its business model and its ability to raise funds for expansion,

Contact us if you have any questions.

AI Workshop 2024 – Redefining Legal, Accounting, and Immigration Services

Explore AI’s impact on legal, accounting, & immigration at AI Workshop 2024.

Navigating the subsidies provided by the South African Government.

Work Abroad Without the Hassle: Your Complete Guide to Work Permit Applications

Explore key steps for successful work permit applications and tips

Interview: Innovation and Leadership w/ Ronan Dunne

Centuro Connect: The World’s First All Encompassing Global Expansion Platform

Tactics to Exploit Your Intellectual Property to Scale and Protect Your Business

Set Up in the UK with the Innovator Founder Visa

Find out how to apply for and secure an Innovator Founder Visa to scale your great idea into a thriving business in the UK

The Remarkable Netflix Global Expansion Journey

The Netflix global expansion journey into over 190 international markets is a phenomenal success. This growth would not have been possible without Netflix’s careful planning and execution. So what are the key lessons that expanding companies seeking to have similar success on a global scale can take from this?

FII Summit in Riyadh: Navigating the Future of Business

Explore our expert analysis on global trends, AI, and sustainable investment for future success from the Future Investment Initiative Summit in Riyadh

Maximising Employee Growth: Training and Development for Globally Mobile Teams

Articles & Webinars

• Comment, Articles & Publications
• Civil Fraud
• International/Offshore
• Arbitration

Riders Not Workers: Status and the Decision in Deliveroo

Unlike last night’s fixture, substitution proved to be the key to success for Deliveroo’s contention that its riders were not workers in Independent Workers Union of Great Britain v Central Arbitration Committee and Deliveroo [2021] EWCA Civ 952 .

This result appears to run counter to the apparent trend of extending employment protections, primarily through findings of “worker” status, to the gig economy. Why, then did Deliveroo reach a different result to Uber , and are there any wider lessons to be drawn from this episode?

The Case in Deliveroo

Unlike the other principal cases that have considered the employment status of gig economy workers, the underlying litigation in Deliveroo was not an employment tribunal case involving named Claimants asserting a particular status to claim personal employment rights. Rather, it was an application made to the Central Arbitration Committee by the Independent Workers Union of Great Britain (IWGB), a trade union, to be recognised as the relevant union for collective bargaining purposes in a particular Deliveroo delivery zone.

A trade union has to seek recognition on behalf of workers for such an application to succeed. The definition of worker for such an application ‘ is in substantially similar, though not identical, terms to that of “worker” in section 230(3) of the Employment Rights Act 1996 and other employment protection legislation ’ (para 5 of the Court of Appeal’s judgment).

The Central Arbitration Committee decided that the individuals for whom the IWGB sought recognition as the relevant trade union were not workers. In particular, the relevant contract under which the riders were engaged provided them with a relatively unrestricted right to engage a substitute to perform any accepted work. Although substitution was a relatively rare occurrence, the CAC heard evidence, and accepted, that it did take place on occasion in practice and was a genuine right rather than merely an artificial device to defeat a claim. This, in the CAC’s view, was ‘ fatal to the Union’s claim ’: a worker is required to engage in personal performance, and the existence of a genuine right to engage a substitute was fatal to that contention on these facts.

Judicial Review and Appeal

No formal right of appeal lies against a decision of the CAC under the statutory recognition procedure. Any challenge to its conclusions has to be brought via Judicial Review proceedings. The IWGB were granted permission to bring such proceedings on only one ground – whether Article 11 of the European Convention on Human Rights (the right to freedom of association, including ‘ the right to form and join trade unions ’) required an expanded interpretation of the definition of “worker” under this legislation that did not cause cases such as these to require personal service so rigidly.

The Judicial Review brought by the Union failed, and the matter came before the Court of Appeal. Again, the Union failed. Submissions in the case were made by the Union and Deliveroo as an Interested Party, with the CAC remaining neutral.

The Court of Appeal, like the High Court, concluded that there was no requirement to interpret the definition of “worker” more widely for the purposes of Article 11, and on that basis, the conclusion that was reached by the CAC was one that was open to it.

This is an unusual case, and it is worth treating it with considerable caution. The Court of Appeal’s decision is about the extent to which Article 11 required a more expansive definition of “worker” when dealing with trade union rights, rather than any wider consideration of the nature and extent of worker status in the gig economy.

In particular, the Court of Appeal was not concerned with whether the CAC’s findings of fact about the right to perform work via a substitute were correct. The Union was not granted permission to challenge these in the JR proceedings. More importantly, the CAC’s decision (and, it appears, the decision to grant limited permission to bring JR proceedings) predated the Supreme Court’s decision in Uber and ors v Aslam and ors [2021] UKSC 5 . The Court of Appeal (Underhill LJ giving the lead judgment) went out of its way to avoid expressing any view either way on whether it would have allowed a broader challenge to the CAC’s findings. Indeed, Coulson LJ, in a short concurring judgment, expressly held out that ‘ there may be other cases where, on different facts and with a broader range of available arguments, a different result might eventuate ’, and went on to identify a number of factors that indicate that this decision might be of relatively limited applicability.

This case is therefore unlikely to be one that advances the debate about employment rights in the gig economy particularly far, nor should it be viewed as deviating from the Supreme Court’s approach in Uber . However, it does restate, in terms that go beyond simply this particular case, the principle that a genuine and broad right to appoint a substitute can (in the right case) defeat the requirement for personal service essential to worker status.

Commentary by Benjamin Gray

Related Members

Deliveroo is an award-winning on-demand delivery service founded in 2013 by William Shu and Greg Orlowski. Deliveroo works with over 16,000 restaurants, as well as over 20,000 riders to provide the best food delivery experience in the world. Deliveroo is headquartered in London, with more than 1,000 employees in offices around the globe, and now operates in over 130 cities across 12 countries, including Australia, Belgium, France, Germany, Hong Kong, Italy, Ireland, Netherlands, Singapore, Spain, United Arab Emirates, and the United Kingdom.

deliveroo.co.uk Industry: Ecommerce Location: London, UK Customer since: 2016

Favorite features Custom VCL Origin Shield TLS termination

Customers all across the world rely on Deliveroo to find and order great food from their favorite restaurants. In a given area, there may be as many as 300 restaurants to choose from, and it’s critical that Deliveroo not only provides these choices quickly, but has the power to swiftly and securely move customers through the ordering process. The Deliveroo team wanted to enhance their previous CDN solution and they found that Fastly’s CDN resulted in 7% improvement in global load time (and in some areas as much as 50%), translating to a 1% increase in site conversion.

Ultimate customization + scaling

Deliveroo needed to create redundancy to prepare for major spikes in demand as a result of restaurant promotions, or peak dining hours, but didn’t want to maintain servers that would mostly sit idle. Fastly empowers Deliveroo to scale when necessary while also giving them the ability to tailor their CDN configuration based on what they needed — such as setting up custom headers to migrate their restaurant order managers from their previous setup.

Reduced load times for global growth

Deliveroo’s global user base is growing significantly, and they wanted the ability to meet demand no matter where requests originate. With Fastly, they’re able to provide consistently fast experiences across the world.

Secure online ordering

Deliveroo handles personal information — such as customer names, emails, and addresses —to ensure smooth online ordering and delivery, and needs to protect their customers’ privacy.

With Fastly, Deliveroo can terminate Transport Layer Security (TLS) at the edge of the network, ensuring fast and secure dining experiences.

“Fastly absolutely helps ensure our customers are getting the best experience by allowing them to find the restaurant they want and check out as fast as possible.” Martin Phee Senior Software Engineer, Deliveroo

“Even the slightest improvement in site performance and conversion has a major impact on our bottom line. By allowing us to meet customer expectations online, Fastly helps drive revenue and growth.” Dan Webb VP of Engineering, Deliveroo

“Fastly enabled us to scale and customize our unique configuration based on our needs, giving us much better throughput and redundancy.” Martin Phee Senior Software Engineer, Deliveroo

“After switching to Fastly, time to first byte (TTFB) went down substantially, and any time we turn up a specific country on Fastly the site responsiveness is dramatic.” Martin Phee Senior Software Engineer, Deliveroo

“With the number and strategic placement of Fastly’s edge servers, we’ve really seen increased site speed as compared to our previous provider. Deliveroo is very JavaScript heavy, so any improvement in those page load times makes a huge difference for the end user.” Martin Phee Senior Software Engineer, Deliveroo

“Fastly maintains all of our TLS certificates, making sure everything is up to date. Because we handle a lot of personal customer information, it’s critical that we have secure solutions in place to protect their privacy.” Martin Phee Senior Software Engineer, Deliveroo

“Fastly has worked out great; being able to manage our own configuration plus having the support we needed to get going was amazing. The Fastly support team got us up and running quickly, building us custom configurations to make for a smooth and painless migration.” Martin Phee Senior Software Engineer, Deliveroo

“Migrating to Fastly was utterly painless — it’s great working with a group of knowledgeable, responsive individuals whether you’re engaging with sales or support.” Dan Webb VP of Engineering, Deliveroo

Ready to get started?

Get in touch or create an account.

• Edge Cloud Platform
• Try Fastly Free
• Network Map
• Professional Services
• Managed CDN
• Support Plans
• Talk to an Expert
• Documentation
• Resource Library
• Support Center
• Network Status
• Customer Stories
• Investor Relations
• Terms of Service
• Privacy policy
• Acceptable Use

• Open access
• Published: 20 June 2024

Association of interleukin-2 and interleukin-10 with the pathophysiology and development of generalized anxiety disorder: a case-control study

• Nisat Sarmin 1   na1 ,
• A. S. M. Roknuzzaman 2   na1 ,
• Rapty Sarker 1   na1 ,
• Mamun -or-Rashid 1 ,
• MMA Shalahuddin Qusar 3 ,
• Sitesh Chandra Bachar 4 ,
• Eva Rahman Kabir 5 ,
• Md. Rabiul Islam 5 &
• Zobaer Al Mahmud 1  

BMC Psychiatry volume  24 , Article number:  462 ( 2024 ) Cite this article

534 Accesses

Metrics details

Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that pro-inflammatory cytokines and chemokines are potential contributors to the pathogenesis of GAD. Here, we aimed to assess the role of interleukin-2 (IL-2) and interleukin-10 (IL-10) in the pathophysiology and development of GAD.

This study recruited 50 GAD patients diagnosed according to the DSM-5 criteria and 38 age-sex-matched healthy controls (HCs). A qualified psychiatrist evaluated all study subjects. The socio-demographic and clinical characteristics of the study population were determined using pre-structured questionnaires or interviews, and cytokine serum levels were estimated using commercially available ELISA kits.

We observed reduced serum IL-10 levels in GAD patients compared to HCs (33.69 ± 1.37 pg/ml vs. 44.12 ± 3.16 pg/ml). Also, we observed a significant negative correlation between altered IL-10 levels and GAD-7 scores ( r =-0.315, p  = 0.039). Moreover, IL-10 serum measurement exhibited good predictive value in receiver operating characteristics (ROC) analysis with an area under the curve (AUC) value of 0.793 ( p  < 0.001) with 80.65% sensitivity and 62.79% specificity at a cutoff value of 33.93 pg/ml. Conversely, we noticed elevated serum IL-2 levels in GAD patients than in HCs (14.81 ± 2.88 pg/ml vs. 8.08 ± 1.1 pg/ml); however, it failed to maintain any significant association with GAD-7 scores, implying that IL-2 might not be involved in GAD pathogenesis. The lower AUC value (0.640; p  > 0.05) exhibited by IL-2 serum measurement in ROC analysis further supported that IL-2 might not be associated with GAD.

This study provides new insights into the complex interplay between anti-inflammatory cytokines and GAD pathogenesis. Based on the present findings, we can assume that IL-10 but not IL-2 may be associated with the pathophysiology and development of GAD. However, further research with a larger population size and longitudinal design is required to confirm the potential diagnostic efficacy of IL-10.

Peer Review reports

Generalized anxiety disorder (GAD) is a chronic neuropsychiatric disorder characterized by persistent and excessive uncontrollable fear or worry (occurs for at least 6 months) about various aspects/activities of daily life, affecting the educational, occupational, or social lives of the affected people [ 1 ]. If a person is excessively worried about anything for most days over at least 6 months, he/she is considered to have GAD. Though currently the prevalence rate of GAD is 3–6% worldwide [ 1 , 2 , 3 ], the prevalence is increasing day by day due to the complexity of modern lifestyles and thus warrants attention from national and international authorities to take interventions for mitigating and managing this disorder properly. If it remains undiagnosed or untreated, the uncontrollable and persistently intense anxiety can lead to a marked reduction in cognitive functions or a reduced capacity to work properly in all spheres of life, including educational, family, social, and individual routine work. As such, chronic GAD leads to a reduced quality of life and thereby poses a significant mental health concern globally.

Despite its high prevalence, significant morbidity, and socioeconomic burden, GAD remains poorly characterized in terms of its pathophysiology or effective treatment options. Though the precise cause and mechanism of pathogenesis are still unknown, evidence suggests that multiple factors, including disrupted serotonergic, dopaminergic, and GABAergic neurotransmission and excessive glutamatergic neurotransmission in the brain, genetic factors, family or environmental stress, chronic diseases, hyperthyroidism, childhood trauma, and special personality traits, are linked to GAD. Alterations in monoaminergic neurotransmissions in limbic systems (cingulate gyrus, hippocampus, amygdala, thalamus, and hypothalamus) due to the lower synaptic availability of serotonin, norepinephrine, and dopamine are thought to be associated with anxiety symptoms. Besides, decreased GABA-mediated inhibitory neurotransmission in the amygdala or excessive activation of excitatory glutamatergic neurotransmission are also suggested to be involved in GAD pathology.

Currently, available pharmacotherapies for GAD include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), pregabalin, and benzodiazepines, which act by reversing these altered monoaminergic neurotransmitter systems. Alongside these drug treatments, non-pharmacological therapies such as several psychological interventions, including cognitive-behavioral therapy, and the acquisition and application of stress management skills, including relaxation and mindfulness skills are also widely used for the management of GAD. However, currently, available pharmacotherapies (SSRIs, SNRIs, pregabalin, and benzodiazepines) have failed to demonstrate the required efficacy in treating anxiety disorders, as 50% of patients failed to respond to these drugs, and at least in 30% of cases, there is a recurrence of the disease following the pharmacological treatment [ 1 , 4 , 5 ]. Moreover, studies reported a higher rate of discontinuity from these pharmacotherapies with low patient adherence or compliance due to the adverse effects, including sexual dysfunction for SSRIs and SNRIs, nausea and dizziness for pregabalin, demonstrating an urgent need for searching for novel anxiolytics [ 3 ]. These findings raised questions about the validity of the currently available mechanism of pathogenesis and suggested that the altered monoaminergic neurotransmitter system might not fully explain the molecular mechanism of GAD development, suggesting other pathophysiological factors might be involved in GAD. Recently, dysregulated immune systems have attracted great interest as an important pathophysiological factor for the development of GAD [ 4 , 6 , 7 , 8 ]. Several clinical and preclinical studies suggest a link between the altered immune system and GAD pathology. Preclinical studies in mice also demonstrated that administration of pro-inflammatory cytokines (including IL-1β, TNF-α, and IL-6) in mice resulted in anxiety-like behaviors that were attenuated or normalized after injecting either anti-inflammatory cytokines or antagonists for the concerned cytokines [ 9 , 10 , 11 , 12 , 13 ]. A recent prospective cohort study conducted by Hou et al., (2019) demonstrated that administration of selective serotonin reuptake inhibitors (escitalopram or sertraline) resulted in a significant reduction in peripheral pro-inflammatory cytokines, and the authors suggested that the anxiolytic effects of these SSRIs might partly be based on their acute anti-inflammatory activities [ 14 ], implicating a significant association between dysregulated peripheral immune systems and GAD development. The development of anxiety-like symptoms in IL-4 gene knock-out mice, reduced levels of IL-4 in anxious mice, and the significant attenuation of anxiety-like behaviors following IL-4 injection demonstrated a positive association between anti-inflammatory cytokines, IL-4 levels, and anxiety pathology [ 15 , 16 , 17 , 18 ]. This immune hypothesis of GAD development is further potentiated by findings from several clinical studies that reported that GAD patients showed significantly higher levels of pro-inflammatory cytokines ( IL-1Ra, IL-1, IL-6, TNF-α, etc.) compared to healthy controls (HCs) [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] along with decreased levels of anti-inflammatory cytokines, including IL-4 and IL-10 [ 25 ]. Besides, pro-inflammatory cytokines such as TNF-α, and IL-6 were significantly associated with anxiety scores [ 29 ]. Consistent with this, a randomized clinical trial in humans demonstrated that LPS administration resulted in enhanced anxiety scores, and the authors suggested a significant correlation between pro-inflammatory cytokine levels and anxiety severity [ 30 ]. LPS-mediated microglia activation causes enhanced release of excessive pro-inflammatory cytokines in the basolateral amygdala, which ultimately leads to neuroinflammation in mice, resulting in the development of anxiety and depression-like behaviors by modulating neuronal plasticity. The authors found that anxiety pathogenesis was due to the excessive release of excitatory neurotransmitter glutamate from presynaptic axonal terminals of the prefrontal cortex, leading to neuroplasticity [ 31 ]. However, some studies reported either no significant variation in pro-inflammatory or anti-inflammatory cytokine serum levels between GAD patients and HCs [ 32 ] or that pro-inflammatory cytokines including IL-1, IL-2, and IL-6 were significantly reduced in GAD patients than HCs [ 33 , 34 ]. This discrepancy in altered levels of inflammatory cytokines across clinical studies necessitates a further examination of the role of these cytokines in GAD pathophysiology.

Interleukin-2 (IL-2) is one of the major pro-inflammatory cytokines implicated in T cell activation, proliferation, and differentiation and is thus linked to excessive neuro-inflammatory processes [ 35 ]. IL-2 has been shown to impair synaptic plasticity and cause neuroinflammation, which ultimately leads to neuronal damage in neurocircuits associated with fear and anxiety signal transduction. IL-2 was also reported to act as a potent modulator of NMDA and kainite-mediated excitability in mesolimbic or mesostriatal systems [ 36 , 37 , 38 ] and thus affect neuroplasticity. As IL-2 was found to be positively associated with major depressive disorder [ 38 , 39 ], probably, IL-2 might also be correlated with anxiety disorders like GAD, as MDD and GAD are highly co-morbid themselves and thus might share common pathophysiological factors. Recently, a preclinical study conducted by Gilio et al., (2022) observed that IL-2 administration in experimentally healthy mice triggered marked anxiety and depression-like behaviors, and the authors suggested that inhibition of GABA-mediated synaptic inhibitory neurotransmission was involved in the pathology of anxiety [ 40 ].

Interleukin-10 (IL-10) is one of the major anti-inflammatory cytokines that is secreted from Treg cells, Th2 cells, CD4 + T cells, CD8 + T cells, monocytes, macrophages, dendritic cells, B cells, neutrophils in the peripheral nervous system, and from microglia, astrocytes in the central nervous system (CNS) [ 41 ]. IL-10 signaling triggers anti-inflammatory, immunosuppressive, and immunoregulatory activities, including downregulating the production and secretion of pro-inflammatory cytokines and chemokines from activated macrophages, neutrophils, mast cells, Th1 cells, and DCS, decreasing the expression of MHC class II and co-stimulatory molecules on macrophages, and thereby suppressing the antigen presentation capacity of APCS [ 42 , 43 , 44 , 45 , 46 ]. In the CNS, it inhibits the production of such cytokines and chemokines by activated microglia and thereby counteracts cellular and tissue damage in response to excessive neuroinflammation [ 47 , 48 ]. IL-10 has also been shown to stimulate axonal regeneration and activate wound healing through tissue repair [ 48 ]. Research also indicates its role as an inhibitor for microglial hyperactivation in response to LPS-induced inflammatory stimulus [ 49 ]. Based on its anti-inflammatory and immunoregulatory functions, researchers suggested an intricate role for IL-10 in several auto-immune and neuropsychiatric disorders. For example, Mesquita et al., (2008) observed that IL-10 KO mice developed markedly enhanced depressive-like behavior, which was attenuated after IL-10 administration, and that overexpression of IL-10 resulted in reduced depressive behaviors in mice [ 50 ]. Moreover, administration of IL-10 into rats attenuated the pro-inflammatory cytokine IL-1β-induced anxiety-like symptoms in male rats [ 10 ], demonstrating that IL-10 possesses anxiolytic activities. Preclinical research using an experimental animal model also suggests that the observed anxiolytic effect of several anti-anxiety drugs, including 3’-deoxyadenosine (3’-dA), imipramine, fluoxetine, and chlordiazepoxide, stems from their ability to upregulate anti-inflammatory cytokine (IL-4, IL-10) expression in the prefrontal cortex and locus coeruleus and simultaneous down-regulation of proinflammatory cytokine gene expression, leading to a correction of the imbalance between proinflammatory and anti-inflammatory states [ 51 , 52 ]. Though several preclinical studies suggest a potential link between IL-10 levels and anxiety disorder, there is a scarcity of clinical studies aimed at evaluating such an association between IL-10 and GAD development [ 10 ].

Currently, there is no objective and cost-effective diagnostic or prognostic biomarker for GAD, which poses challenges in early diagnosis or risk prediction and leads to misdiagnosis or underdiagnosis, hampering the proper management of the disease. Currently available diagnostic tools, including self-reported symptoms and scoring severity based on the patient’s response to the 7-item questionnaire (GAD-7 scores), are subjective. Though neuroimaging techniques such as positron emission tomography (PET) and functional MRI can be used for the proper and objective diagnosis of GAD, due to their high cost and sophistication or complexities, these diagnostic tools are not suitable for either mass-level screening or are not easy to conduct multiple times to monitor the disease progression or therapeutic drug response. As such, the investigation of cost-effective objective biomarkers for GAD is one of the major focuses of current research on GAD. Finding a suitable biomarker is essential for early diagnosis and initiating psychotherapy and pharmacotherapy as early as possible [ 3 ]. Several studies were performed investigating the potential association between altered pro-inflammatory cytokines or anti-inflammatory cytokines and the pathogenesis of GAD. However, the actual role of inflammatory cytokines in GAD patients is not well explained. Therefore, the present study aims to explore the role of pro-inflammatory cytokines (IL-2) and anti-inflammatory cytokines (IL-10) in the pathophysiology and development of GAD. Also, we aim to find the potential associations of IL-2 and IL-10 with the severity of GAD patients. We believe the present study results would help to understand the pathophysiology and development of GAD.

Study population

We recruited 88 participants for this case-control study (50 GAD patients and 38 HCs matched by age and sex). Patients were collected from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh, and HCs from nearby areas of Dhaka city. A professional psychiatrist diagnosed patients and evaluated HCs based on DSM-5 criteria. We applied a 7-item GAD scale to assess the severity of anxiety symptoms [ 53 ]. The total scores range from 0 to 21, and it classifies the anxiety severity into four categories: minimal anxiety (0–4 scores), mild anxiety (5–9 scores), moderate anxiety (10–14 scores), and severe anxiety (15–21 scores). We excluded subjects with a co-morbidity of other psychiatric disorders, such as MDD, panic disorder, post-traumatic stress disorder, and social phobia, from the study. Additional exclusion criteria for participants were chronic liver and kidney diseases, infectious diseases, and alcohol or substance abuse. We also excluded patients who were exposed to anxiolytics or antidepressant medications within at least two weeks prior to the study that might have an impact on cytokine levels. We recorded the sociodemographic profile of the study population using a pre-designed questionnaire. The objectives of the study were explained to each participant, and informed written consent was obtained from them before their participation in this study. The study was conducted in accordance with the Declaration of Helsinki.

Blood sample collection and serum isolation

A 5 ml blood sample was collected from the cephalic vein of each participant. The blood samples were kept at room temperature for 1 hour to ensure coagulation and were then subjected to centrifugation at 3000 rpm for 15 minutes at room temperature to collect serum samples. The collected serum was then placed in the Eppendorf tube and stored at -80 °C until further analysis.

Estimation of serum cytokine levels

We estimated the serum levels of IL-2 and IL-10 by ELISA methods (Boster Bio, USA). We followed the manufacturer’s protocol for the ELISA assays. At first, we added 100 µl of standard cytokine solution, samples, and controls to each well of a pre-coated 96-well microplate. The microplates were covered with a plate sealer and incubated for 90 min at 37⁰C. After that, the cover was removed, and the liquid in each well was discarded. Subsequently, 100 µl of biotinylated anti-IL-2 antibody or anti-IL-10 antibody was incorporated into each well and incubated for 60 min at 37⁰C. After discarding the liquid from each well and washing it three times with 300 µl of wash buffer, 100 µl of avidin-biotin-peroxidase complex was added to each well, and the microplate was then again incubated for 30 min at 37⁰C. After the incubation period, the liquid was again discarded, and the plate was washed again with 300 µl of wash buffer five times. Following the addition of 90 µl color-developing reagent (TMB) into each well, the plate was incubated in a dark place for 30 min at RT, followed by the addition of 90 µl of stop solution to each well to stop the reaction process. We measured the absorbance with a microplate reader at 450 nm. We calculated the cytokine levels using standard curves and expressed them as pg/ml.

Data presentation and statistical analysis

GraphPad Prism (version 8.0.1) and Statistical Package for the Social Sciences (version 24.0) were used for data analysis. We used descriptive statistics to find the variations in sociodemographic profiles and clinical characteristics between the groups. A T-test and a Chi-square test were employed to determine the statistical level of significance between the mean differences for variables across patients versus HC groups in the case of continuous variables and categorical variables, respectively. We used boxplot graphs for comparisons of analyzed cytokines between patients and HCs. We also generated scatter plot graphs for several clinical variables in GAD patients to show the correlations among the clinical parameters. A correlation analysis was performed to assess the potential association between several demographic and clinical variables in GAD patients. Receiver operating characteristics (ROC) analysis was conducted to determine the diagnostic efficacy of serum IL-2 or IL-10 levels in discriminating GAD patients from HCs. In all cases, statistical significance was considered at p  < 0.05.

Sociodemographic characteristics of the study population

The sociodemographic characteristics of the study population are presented in Table  1 . The GAD patients and HCs were similar in terms of their age, sex, and BMI. Among the participants, about 60% were male and from urban areas. The majority of patients (60.00%) and HCs (68.42%) were unmarried. There was no significant variation between patients and HCs for their education level, occupation, economic status, or smoking status. In contrast, there was a difference between patients and HCs for their family history and previous history of the disease. In GAD patients, 20.00% had a family history, and 40.00% had a previous history of the disease.

Clinical characteristics and laboratory findings

Clinical characteristics and laboratory analysis results are presented in Table  2 . GAD patients displayed markedly higher serum levels of IL-2 (14.81 ± 2.88 pg/ml) compared to HCs (8.08 ± 1.10 pg/ml), and the difference reached the statistically significant level ( p  = 0.037, two-tailed unpaired t-test) (Table  2 ; Fig.  1 ). Though male GAD patients exhibited markedly higher levels of IL-2 compared to male HCs ( p  = 0.048), there was no significant variation in IL-2 levels between female patients and female HCs ( p  > 0.05) (Fig.  1 ). Though some 1.8-fold higher IL-2 serum levels were observed in male GAD patients compared to female GAD patients, the difference did not reach the statistical significance level ( p  = 0.198, two-tailed unpaired t-test). In contrast to the results obtained for IL-2, IL-10 showed a statistically significant ( p  < 0.001) reduction in GAD patients (33.69 ± 1.37 pg/ml) compared to HCs (44.12 ± 3.16 pg/ml) (Fig.  1 ). Similar to the results obtained for IL-2, IL-10 levels showed a statistically significant difference between patients versus HCs when male people were considered (Fig.  1 ). In contrast, there was no significant variation in IL-10 levels between female GAD patients and female HCs ( p  > 0.05).

Distribution of serum IL-2 ( a i ) and IL-10 ( b i ) levels in GAD patients and healthy controls. Comparison of IL-2 and IL-10 levels between GAD patients and their counterparts in control subjects are showed in a i and b i . Comparison of IL-2 and IL-10 levels between male or female GAD patients and their counterparts in control subjects are presented in a ii and b ii

Correlation analysis among different study parameters

We then performed a series of correlation analyses to investigate the association of altered cytokine serum levels with several demographic and clinical variables, such as age, BMI, DSM-5, and GAD-7 scores (Table  3 ). Serum IL-2 levels did not show any positive or negative association with either DSM-5 or GAD-7 scores ( p  > 0.05), suggesting that despite its significant enhancement in GAD patients compared to HCs, IL-2 may not associate with GAD pathophysiology. We also observed no significant association between the ages of the patients and IL-2 serum levels. In contrast, the IL-2 levels of GAD patients maintained a significant and positive correlation with BMI levels of patients ( r  = 0.390, p  < 0.05) which is consistent with the intricate relationship between body mass and enhanced pro-inflammatory responses. Contrary to the results obtained for IL-2, reduced serum IL-10 levels maintained a significant but negative association with both DSM-5 scores ( r =-0.300, p  = 0.045) and GAD-7 scores ( r =-0.315, p  = 0.039), implicating that altered IL-10 levels are linked to GAD development or pathogenesis. However, the age and BMI levels of GAD patients failed to show any positive or negative association with IL-10 serum levels. Analysis also showed a significant and strong positive association between IL-2 and IL-10 serum levels ( r  = 0.471, p  = 0.011) in GAD patients, which might be due to the compensatory enhancement of anti-inflammatory cytokine, IL-10 in response to elevated pro-inflammatory cytokine, IL-2 levels. Also, we displayed these correlations among several clinical variables of GAD patients by scatter plot graphs (Fig.  2 ).

Scatter plot graphs for several clinical variables of GAD patients showing existence or absence of correlation between the clinical parameters. Scatter plot for serum IL-2 levels versus GAD-7 scores ( a ) or DSM-5 scores ( b ) expressing no significant association between IL-2 and both clinical parameters. Scatter plot graphs showing significant association between IL-2 levels and BMI ( c ), IL-10 levels and GAD-7 scores ( d ), IL-10 levels and DSM-5 scores and IL-10 and IL-2 levels ( f )

Receiver operating characteristic curve analysis

Serum IL-10 measurement showed a good performance in differentiating GAD patients from HCs, which was evidenced by its significantly higher area under the curve (AUC) value of 0.793 ( p  < 0.001) with 80.65% sensitivity and 62.79% specificity at a cut-off value of 33.93 pg/ml, in which the cytokine levels below this point indicate disease states (Table  4 ; Fig.  3 ). ROC analysis of serum IL-2 levels failed to discriminate GAD patients from HCs as the AUC value was below the acceptable range (AUC: 0.640; p  = 0.108) with 54.17% sensitivity and 68.18% specificity at a cut-off value of 8.83 pg/ml) (Fig.  3 ; Table  4 ).

Receiver operating characteristic curve (ROC) for serum IL-2 ( a ) and IL-10 levels ( b )

To the best of our knowledge, this is the first case-control study to investigate the potential association between the pathophysiology of GAD and the pro-inflammatory cytokine, IL-2, and the anti-inflammatory cytokine, IL-10, among the Bangladeshi population. We observed that IL-10 serum levels were significantly lower in GAD patients than in HCs, and this reduction was found to be significantly but negatively associated with both DSM-5 scores and GAD-7 scores, demonstrating potential involvement of this anti-inflammatory cytokine in disease severity and symptoms. Our results of a significant reduction in IL-10 levels in GAD patients are in good agreement with those observed in other studies [ 23 , 25 ]. In contrast, our results diverge from those reported by others [ 33 , 54 ] who either reported no significant variation in IL-10 levels between GAD patients and HCs or that IL-10 levels were enhanced in GAD patients compared to HCs. ROC analysis also demonstrated the good predictive value of IL-10 serum measurement in discriminating diseased patients from HCs, suggesting that IL-10 serum level might be a potential biomarker for diagnosis, anti-anxiety drug response monitoring, or disease progression monitoring. Recently, Hou et al. (2019) demonstrated that peripheral serum levels of the pro-inflammatory cytokine IL-6 could be used to monitor the treatment response of SSRIs in GAD [ 14 ]. Similarly, IL-10 might be used as a marker for therapeutic drug monitoring in GAD. However, further longitudinal studies are required to find any causal relationship between IL-10 and disease severity or pathogenesis. On the other hand, serum IL-2 levels were significantly elevated in GAD patients compared to HCs, but they failed to demonstrate any significant association with either DSM-5 scores or GAD-7 scores in Pearson correlation analysis, implying that IL-2 levels might not be associated with the pathophysiology and development of GAD. Consistent with this, ROC analysis showed that IL-2 levels have no significant diagnostic efficacy in differentiating GAD patients from HCs. Further analysis with a larger population size is required to explore the role of IL-2 in the context of GAD severity. Our results are consistent with those reported by Tang et al. (2018), who also observed that GAD patients exhibited significantly higher serum levels of IL-2 compared to HCs [ 19 ]. However, our results are not in agreement with those reported by others who observed either no significant variation in IL-2 levels [ 54 ] or a significant reduction in GAD patients compared to HCs [ 25 , 33 , 34 , 55 ]. We also observed a significant positive correlation between IL-2 and IL-10 levels in GAD patients, which indicates a compensatory mechanism [ 56 ].

Our study provides some valuable insights into the complex and intricate relationship between the dysregulated immune system and GAD. The observed reduction in IL-10 levels in GAD patients in our study suggests a potential immunoregulatory imbalance in GAD, with IL-10 playing a role in modulating anxiety severity. The lack of a significant association between IL-2 serum levels and anxiety severity highlights the nuanced nature of immune dysregulation in GAD, warranting further exploration into the specific mechanisms involved. Elevated levels of pro-inflammatory cytokine, IL-2, and decreased levels of anti-inflammatory cytokine, IL-10, in GAD patients compared to HCs indicate that GAD individuals of the Bangladeshi cohort are characterized by heightened inflammatory responses derived from the imbalance between pro-inflammatory and anti-inflammatory states. Our study finding provides further support for the cytokine hypothesis of anxiety disorder, which proposes that pro-inflammatory cytokine-mediated neuroinflammatory processes can lead to anxiety symptoms or behaviors by downregulating serotonin biosynthesis or enhancing the reuptake of serotonin, resulting in an altered serotonergic neurotransmitter system in the CNS [ 15 ]. The observed significant negative correlation between IL-10 and DSM-5 scores or GAD-7 scores suggests that lowering IL-10 levels might be involved in the pathogenesis of GAD. One of the major implications of our study findings is that IL-10 signaling might be targeted to explore potential novel immunological/immunomodulatory therapies against GAD. The diminished IL-10 levels and their negative correlation with GAD severity suggest a potential avenue for therapeutic intervention. IL-10 might also be used as an anti-inflammatory adjunctive therapy with other pharmacotherapies including SSRIs/SNRIs. However, at this moment, we don’t know the exact mechanism by which lowered levels of IL-10 are linked to higher anxiety severity in GAD patients.

As IL-10 has anti-inflammatory and immunoregulatory activities such as suppression of production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) from microglia and astrocytes, reduction in IL-10 levels in GAD patients in our study led to an imbalance between pro-inflammatory and anti-inflammatory states and resulted in enhanced pro-inflammatory responses, which might be the cause of enhanced anxiety symptoms as inflammatory cytokine-mediated neuroinflammation was reported to be linked with disrupted monoaminergic neurotransmission in the brain. Besides, elevated levels of IL-10 were shown to attenuate anxiety-like behaviors by modulating GABAergic neurotransmission in the amygdala (Patel et al., 2021). IL-10 was also reported to display some neuroprotective activities and has been shown to inhibit neuronal apoptosis and promote neurite outgrowth, axonal outgrowth, and synapse formation in the brain by the JAK1-STAT3 signaling pathway [ 57 ]. In a preclinical study, IL-4 has been shown to cause the shifting of microglia and macrophages from pro-inflammatory to anti-inflammatory neuroprotective phenotypes characterized by excessive production of arginase-1 and PPARγ receptor expression in microglia and macrophage and thereby attenuating brain-injury-mediated anxiety by inhibiting neuronal loss and nerve tracts in the limbic system [ 58 ]. A similar mechanism might be involved in IL-10-mediated anxiety symptom improvement in GAD patients. Further research is required to unravel the exact mechanisms of IL-10-mediated anxiety symptom attenuation in GAD patients.

In terms of diagnostic marker development, as IL-10 serum level measurement demonstrated good performance in discriminating GAD patients from HCs and as IL-10 levels maintained a significant and negative correlation with disease severity, IL-10 serum level raised the possibility of being an objective biomarker for GAD. However, the diagnostic efficacy of this cytokine should be investigated thoroughly using a range of longitudinal studies. Despite this, at this time we can conclude that IL-10 might be used as a risk indicator for assessment of susceptibility to anxiety disorder, resulting in early detection of the disease and prompting the initiation of intervention strategies. This early detection will reduce treatment costs and decrease the prevalence and morbidity associated with this chronic disorder.

The strength of our study is that we designed a set of inclusion and exclusion criteria for the recruitment of participants and followed those criteria in such a way that homogenous population data could be obtained. The strict study design helped us enormously to minimize the potential impact of several confounding variables, including age, sex, BMI, co-morbid diseases, and immunomodulatory drugs, on cytokine levels. However, our study also has some limitations that should be acknowledged. The major limitation of this study is the smaller sample size. We recruited 50 patients and 38 HCs, which does not represent the whole Bangladeshi demographic. It would be better if we could enroll an equal number of cases and controls. For example, we observed that cytokine levels maintained a statistically significant difference between male GAD patients and male HCs. In contrast, no significant variation in cytokine levels was observed when female data were considered. As we have included more male participants (60%) than female participants (40%), the lower sample size of female participants might generate a higher background noise, resulting in lower statistical power, warranting further studies recruiting a larger population size to investigate sex-specific differences in cytokine levels in GAD patients. Our case-control study design is inherently correlational and thus not able to evaluate the causal relationship between altered cytokine levels and GAD. So, at this moment, we cannot conclude whether the altered levels of serum cytokines are the causes of anxiety development or just the outcome of pathophysiological changes.

Longitudinal studies are required to investigate whether altered cytokine levels precede GAD or if it’s just a mere reflection of GAD pathology. Though we have restricted the impacts of several co-variates, other confounding variables, including genetic polymorphism in cytokine genes, the effect of lifestyle or xenobiotics, and dietary habits, were not considered, which might have modulatory effects on serum cytokine levels.

The study provides valuable insights for understanding the pathogenesis of GAD. Despite having elevated IL-2 levels in GAD patients compared to HCs, it failed to demonstrate a significant association with anxiety severity as assessed by GAD-7 scores. In contrast, serum IL-10 levels were significantly reduced in GAD patients compared to HCs and showed a significant negative correlation with anxiety severity, implicating a potential link with the GAD pathophysiology. Our results support the immune hypothesis of GAD development. Our study findings also suggest that IL-10 serum level measurement might offer an objective blood-based biomarker or risk assessment indicator for GAD. We recommend further research employing a larger population size and homogenous data from different areas of Bangladesh to confirm our study findings.

Data availability

All the relevant data and information will be available from the corresponding author upon reasonable request.

Abbreviations

Body mass index

Chronic energy deficiency

Confidence interval

Central nervous system

Diagnostic and statistical manual for mental disorders, 5th edition

Enzyme-linked immunosorbent assay

• Generalized anxiety disorder

Generalized anxiety disorder 7-item scores

Healthy control

• Interleukin-2
• Interleukin-10

Receiver operating characteristic

Standard error mean

Statistical package for social science

Fagan HA, Baldwin DS. Pharmacological treatment of generalised anxiety disorder: current practice and future directions. Expert Rev Neurother. 2023;23(6):535–48. https://doi.org/10.1080/14737175.2023.2211767 .

Article   CAS   PubMed   Google Scholar  

Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. 2018;19(10):1057–70. https://doi.org/10.1080/14656566.2018.1491966 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Maron E, Nutt D. Biological markers of generalized anxiety disorder. Dialogues Clin Neurosci. 2017;19(2):147–58. https://doi.org/10.31887/DCNS.2017.19.2/dnutt .

Article   PubMed   PubMed Central   Google Scholar  

Costello H, Gould RL, Abrol E, Howard R. Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder. BMJ Open. 2019;9:e027925. https://doi.org/10.1136/bmjopen-2018-027925 .

Ansara ED. Management of treatment-resistant generalized anxiety disorder. Ment Health Clin. 2020;5(6):326–34. https://doi.org/10.9740/mhc.2020.11.326 .

Article   Google Scholar  

Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology. 2017;42:254–70. https://doi.org/10.1038/npp.2016.146 .

Renna ME, O’Toole MS, Spaeth PE, Lekander M, Mennin DS. The association between anxiety,traumatic stress, and obsessive-compulsive disorders and chronic inflammation: A systematic review and meta-analysis. Depress Anxiety. 2018;;35(11):1081–1094. doi: 10.1002/da.22790.

Hou R, Baldwin DS. A neuroimmunological perspective on anxiety disorders. Hum Psychopharmacol. 2012;27(1):6–14.

Zhu CB, Lindler KM, Owens AW, Daws LC, Blakely RD, Hewlett WA. Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters. Neuropsychopharmacology. 2010;35:2510–20.

Munshi S, Parrilli V, Rosenkranz JA. Peripheral anti-inflammatory cytokine Interleukin-10 treatment mitigates interleukin-1β - induced anxiety and sickness behaviors in adult male rats. Behav Brain Res. 2019;17:372:112024. https://doi.org/10.1016/j.bbr.2019.112024 .

Article   CAS   Google Scholar  

Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology. 2010;139(6):2102–e21121. https://doi.org/10.1053/j.gastro.2010.06.063 .

Gentile A, Fresegna D, Musella A, Sepman H, Bullitta S, De Vito F et al. Interaction between interleukin-1β and type-1 cannabinoid receptor is involved in anxiety-like behavior in experimental autoimmune encephalomyelitis. J Neuroinflammation. 2016;13(1):231. Published 2016 Sep 2. https://doi.org/10.1186/s12974-016-0682-8 .

Haji N, Mandolesi G, Gentile A, Sacchetti L, Fresegna D, Rossi S, et al. TNF-α-mediated anxiety in a mouse model of multiple sclerosis. Exp Neurol. 2012;237(2):296–303. https://doi.org/10.1016/j.expneurol.2012.07.010 .

Hou R, Ye G, Liu Y, Chen X, Pan M, Zhu F, et al. Effects of SSRIs on peripheral inflammatory cytokines in patients with generalized anxiety disorder. Brain Behav Immun. 2019;81:105–10. https://doi.org/10.1016/j.bbi.2019.06.001 .

Quagliato LA, Nardi AE. Cytokine profile in drug-naïve panic disorder patients. Transl Psychiatry. 2022;12(1):75. https://doi.org/10.1038/s41398-022-01835-y . Published 2022 Feb 22.

Lee HJ, Park HJ, Starkweather A, An K, Shim I. Decreased Interleukin-4 release from the neurons of the Locus Coeruleus in response to immobilization stress. Mediators Inflamm. 2016;2016:3501905. https://doi.org/10.1155/2016/3501905 .

Gao T, Li B, Hou Y, Luo S, Feng L, Nie J, et al. Interleukin-4 signalling pathway underlies the anxiolytic effect induced by 3-deoxyadenosine. Psychopharmacology. 2019;236(10):2959–73. https://doi.org/10.1007/s00213-019-5186-7 .

Moon ML, Joesting JJ, Blevins NA, Lawson MA, Gainey SJ, Towers AE, et al. IL-4 knock out mice display anxiety-like Behavior. Behav Genet. 2015;45(4):451–60. https://doi.org/10.1007/s10519-015-9714-x .

Tang Z, Ye G, Chen X, Pan M, Fu J, Fu T, et al. Peripheral proinflammatory cytokines in Chinese patients with generalised anxiety disorder. J Affect Disord. 2018;225:593–8. https://doi.org/10.1016/j.jad.2017.08.082 .

Yang CJ, Liu D, Xu ZS, Shi SX, Du YJ. The pro-inflammatory cytokines, salivary cortisol and alpha-amylase are associated with generalized anxiety disorder (GAD) in patients with asthma. Neurosci Lett. 2017;656:15–21. https://doi.org/10.1016/j.neulet.2017.07.021 .

Vogelzangs N, Beekman AT, de Jonge P, Penninx BW. Anxiety disorders and inflammation in a large adult cohort. Transl Psychiatry. 2013;3(4):e249. https://doi.org/10.1038/tp.2013.27 .

Vieira MM, Ferreira TB, Pacheco PA, Barros PO, Almeida CR, Araújo-Lima CF, et al. Enhanced Th17 phenotype in individuals with generalized anxiety disorder. J Neuroimmunol. 2010;229(1–2):212–8. https://doi.org/10.1016/j.jneuroim.2010.07.018 .

Hou R, Garner M, Holmes C, Osmond C, Teeling J, Lau L, et al. Peripheral inflammatory cytokines and immune balance in generalised anxiety disorder: case-controlled study. Brain Behav Immun. 2017;62:212–8. https://doi.org/10.1016/j.bbi.2017.01.021 .

Copeland WE, Shanahan L, Worthman C, Angold A, Costello EJ. Generalized anxiety and C-reactive protein levels: a prospective, longitudinal analysis. Psychol Med. 2012;42(12):2641–50. https://doi.org/10.1017/S0033291712000554 .

Ferreira TB, Kasahara TM, Barros PO, Vieira MM, Bittencourt VC, Hygino J, et al. Dopamine up-regulates Th17 phenotype from individuals with generalized anxiety disorder. J Neuroimmunol. 2011;238(1–2):58–66. https://doi.org/10.1016/j.jneuroim.2011.06.009 .

Bankier B, Barajas J, Martinez-Rumayor A, Januzzi JL. Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients. Eur Heart J. 2008;29(18):2212–7. https://doi.org/10.1093/eurheartj/ehn326 .

Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine. 1998;10(4):313–8. https://doi.org/10.1006/cyto.1997.0290 .

Lu H, Yang Q, Zhang Y. The relation of common inflammatory cytokines with anxiety and depression and their values in estimating cardiovascular outcomes in coronary heart disease patients. J Clin Lab Anal. 2022;36(6):e24404. https://doi.org/10.1002/jcla.24404 .

Pitsavos C, Panagiotakos DB, Papageorgiou C, Tsetsekou E, Soldatos C, Stefanadis C. Anxiety in relation to inflammation and coagulation markers, among healthy adults: the ATTICA study. Atherosclerosis. 2006;185(2):320–6. https://doi.org/10.1016/j.atherosclerosis.2005.06.001 .

Lasselin J, Elsenbruch S, Lekander M, Axelsson J, Karshikoff B, Grigoleit JS, et al. Mood disturbance during experimental endotoxemia: predictors of state anxiety as a psychological component of sickness behavior. Brain Behav Immun. 2016;57:30–7. https://doi.org/10.1016/j.bbi.2016.01.003 .

Article   PubMed   Google Scholar  

Zheng ZH, Tu JL, Li XH, Hua Q, Liu WZ, Liu Y, et al. Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala. Brain Behav Immun. 2021;91:505–18. https://doi.org/10.1016/j.bbi.2020.11.007 .

Mongan D, Raj SS, Föcking M, Byrne JF, Zammit S, Cannon M, et al. Associations between plasma inflammatory markers and psychotic disorder, depressive disorder and generalised anxiety disorder in early adulthood: a nested case-control study. Brain Behav Immun. 2023;111:90–100. https://doi.org/10.1016/j.bbi.2023.03.025 .

Shen Z, Cui L, Mou S, Ren L, Yuan Y, Shen X, et al. Combining S100B and cytokines as neuro-inflammatory biomarkers for diagnosing generalized anxiety disorder: a proof-of-Concept Study based on machine learning. Front Psychiatry. 2022;13:881241. https://doi.org/10.3389/fpsyt.2022.881241 . Published 2022 Jun 22.

Wagner EN, Strippoli MF, Ajdacic-Gross V, Gholam-Rezaee M, Glaus J, Vandeleur C, et al. Generalized anxiety disorder is prospectively Associated with decreased levels of Interleukin-6 and Adiponectin among individuals from the community. J Affect Disord. 2020;270:114–7. https://doi.org/10.1016/j.jad.2020.03.123 .

Ross SH, Cantrell DA. Signaling and function of Interleukin-2 in T lymphocytes. Annu Rev Immunol. 2018;36:411–33. https://doi.org/10.1146/annurev-immunol-042617-053352 .

Ye JH, Tao L, Zalcman SS. Interleukin-2 modulates N-methyl-D-aspartate receptors of native mesolimbic neurons. Brain Res. 2001;894(2):241–8. https://doi.org/10.1016/s0006-8993(01)02056-x .

Ye JH, Zalcman SS, Tao L. Kainate-activated currents in the ventral tegmental area of neonatal rats are modulated by interleukin-2. Brain Res. 2005;1049(2):227–33. https://doi.org/10.1016/j.brainres.2005.05.016 .

Suhee FI, Shahriar M, Islam SMA, Bhuiyan MA, Islam MR. Elevated serum IL-2 levels are Associated with Major Depressive disorder: a case-control study. Clin Pathol. 2023;16:2632010X231180797. https://doi.org/10.1177/2632010X231180797 .

Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017;135(5):373–87. https://doi.org/10.1111/acps.12698 .

Gilio L, Fresegna D, Gentile A, Guadalupi L, Sanna K, De Vito F, et al. Preventive exercise attenuates IL-2-driven mood disorders in multiple sclerosis. Neurobiol Dis. 2022;172:105817. https://doi.org/10.1016/j.nbd.2022.105817 .

Carlini V, Noonan DM, Abdalalem E, Goletti D, Sansone C, Calabrone L, et al. The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions. Front Immunol. 2023;14:1161067. https://doi.org/10.3389/fimmu.2023.1161067 . Published 2023 Jun 8.

Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170(6):2081–95. https://doi.org/10.1084/jem.170.6.2081 .

Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991;147(11):3815–22.

Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991;146(10):3444–51.

Bogdan C, Vodovotz Y, Nathan C. Macrophage deactivation by interleukin 10. J Exp Med. 1991;174(6):1549–55. https://doi.org/10.1084/jem.174.6.1549 .

Murray PJ. The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription. Proc Natl Acad Sci U S A. 2005;102(24):8686–91. https://doi.org/10.1073/pnas.0500419102 .

Lobo-Silva D, Carriche GM, Castro AG, Roque S, Saraiva M. Balancing the immune response in the brain: IL-10 and its regulation. J Neuroinflammation. 2016;13(1):297. https://doi.org/10.1186/s12974-016-0763-8 .

Saraiva M, Vieira P, O’Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med. 2020;217(1):e20190418. https://doi.org/10.1084/jem.20190418 .

Shemer A, Scheyltjens I, Frumer GR, Kim JS, Grozovski J, Ayanaw S, et al. Interleukin-10 prevents pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge. Immunity. 2020;53(5):1033–e10497. https://doi.org/10.1016/j.immuni.2020.09.018 .

Mesquita AR, Correia-Neves M, Roque S, Castro AG, Vieira P, Pedrosa J, et al. IL-10 modulates depressive-like behavior. J Psychiatr Res. 2008;43(2):89–97. https://doi.org/10.1016/j.jpsychires.2008.02.004 .

Obuchowicz E, Bielecka AM, Paul-Samojedny M, Pudełko A, Kowalski J. Imipramine and fluoxetine inhibit LPS-induced activation and affect morphology of microglial cells in the rat glial culture. Pharmacol Rep. 2014;66(1):34–43. https://doi.org/10.1016/j.pharep.2013.08.002 .

Blatteau JE, de Maistre S, Lambrechts K, Abraini J, Risso JJ, Vallée N. Fluoxetine stimulates anti-inflammatory IL-10 cytokine production and attenuates sensory deficits in a rat model of decompression sickness. J Appl Physiol (1985). 2015;119(12):1393–9. https://doi.org/10.1152/japplphysiol.00602.2015 .

Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7. https://doi.org/10.1001/archinte.166.10.1092 .

Tofani T, Mannelli LD, Zanardelli M, et al. An immunologic profile study in drug-naive generalized anxiety non depressed patients: a pilot study. Eur Neuropsychopharmacol. 2015;25(suppl 2):S226.

Koh KB, Lee BK. Reduced lymphocyte proliferation and interleukin-2 production in anxiety disorders. Psychosom Med. 1998;60(4):479–83.

Inaba A, Tuong ZK, Zhao TX, et al. Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells. Nat Commun. 2023;14(1):2071. https://doi.org/10.1038/s41467-023-37424-w . Published 2023 Apr 12.

Chen H, Lin W, Zhang Y, Lin L, Chen J, Zeng Y, et al. IL-10 promotes neurite outgrowth and synapse formation in cultured cortical neurons after the oxygen-glucose deprivation via JAK1/STAT3 pathway. Sci Rep. 2016;6:30459. https://doi.org/10.1038/srep30459 . Published 2016 Jul 26.

Pu H, Wang Y, Yang T, Leak RK, Stetler RA, Yu F, et al. Interleukin-4 mitigates anxiety-like behavior and loss of neurons and fiber tracts in limbic structures in a microglial PPARγ-dependent manner after traumatic brain injury. Neurobiol Dis. 2023;180:106078. https://doi.org/10.1016/j.nbd.2023.106078 .

Download references

Acknowledgements

The authors are thankful to all the participants of this study. They are also thankful to the staff and physicians at the Department of Psychiatry, BSMMU, for their technical and administrative support. The authors are also thankful for the laboratory support provided by the Department of Pharmacy, University of Asia Pacific, Dhaka Bangladesh.

This research received no specific grant from any funding agency. However, we received partial funding from University of Dhaka, Bangladesh (Centennial Research grant (2nd Phase) for the year of 2020–2021, project title: “Investigation of peripheral pro-inflammatory and anti-inflammatory cytokines and immune balance in Bangladeshi patients with Generalized Anxiety Disorder”).

Author information

Nisat Sarmin, A. S. M. Roknuzzaman and Rapty Sarker contributed equally to this work.

Authors and Affiliations

Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh

Nisat Sarmin, Rapty Sarker, Mamun -or-Rashid & Zobaer Al Mahmud

Department of Pharmacy, University of Asia Pacific, Dhaka, 1205, Bangladesh

A. S. M. Roknuzzaman

Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University, Shahabagh, Dhaka, 1000, Bangladesh

MMA Shalahuddin Qusar

Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh

Sitesh Chandra Bachar

School of Pharmacy, BRAC University, Kha 224 Bir Uttam Rafiqul Islam Avenue, Merul Badda, Dhaka, 1212, Bangladesh

Eva Rahman Kabir & Md. Rabiul Islam

You can also search for this author in PubMed   Google Scholar

Contributions

NS, ASMR, RS, MRI, and ZAM: Conceptualization, Data curation, Investigation, Writing – original draft. MR, MMASQ, SCB, and ZAM: Funding acquisition, Project administration, Validation. ERK, MRI, and ZAM: Conceptualization, Formal analysis, Methodology, Supervision, Writing – review & editing.

Corresponding authors

Correspondence to Md. Rabiul Islam or Zobaer Al Mahmud .

Ethics declarations

Ethics approval and consent to participate.

The research protocol was approved by the Research Ethics Committee (REC) of the University of Asia Pacific, Dhaka, Bangladesh (Ref: UAP/REC/2023/202-S). We briefed the objectives of the study to the participants, and informed consent was obtained from each of them. We conducted this investigation following the Helsinki Declaration’s guiding principles.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Sarmin, N., Roknuzzaman, A.S.M., Sarker, R. et al. Association of interleukin-2 and interleukin-10 with the pathophysiology and development of generalized anxiety disorder: a case-control study. BMC Psychiatry 24 , 462 (2024). https://doi.org/10.1186/s12888-024-05911-z

Download citation

Received : 31 December 2023

Accepted : 13 June 2024

Published : 20 June 2024

DOI : https://doi.org/10.1186/s12888-024-05911-z

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Mental disorders

BMC Psychiatry

ISSN: 1471-244X

• Submission enquiries: [email protected]
• General enquiries: [email protected]