Could Chronic Stress Change How Your Body Controls Inflammation?

We hear so much about the dangers of high cortisol, but what happens when the hormone that helps control inflammation isn’t working as it should?

When people come to see me about their autoimmune condition, stress is often part of the conversation. Sometimes they can identify a particularly stressful period before their symptoms first appeared. For others, they notice their symptoms become worse during demanding periods at work, following an illness or when they’ve been struggling with their sleep.

And sometimes the stress comes from living with the condition itself.

Having experienced autoimmune disease from childhood, and later post-viral chronic fatigue syndrome, I understand how frustrating it can be when you’re trying to improve your health but your body doesn’t seem to be responding in the way you’d hoped.

One of the things I find particularly interesting is that stress doesn’t simply affect how we feel emotionally. It can also influence the way our immune system behaves.

Most of us have heard of cortisol, usually described as the body’s main stress hormone. It’s often presented as something we should be trying to lower, particularly if we’re experiencing fatigue, poor sleep, weight changes or inflammation.

But there’s another side to cortisol that I think deserves much more attention.

Cortisol is one of the hormones that helps our body control inflammation. And when we experience prolonged stress or ongoing inflammation, the way our body produces and responds to cortisol can sometimes change.

This is particularly interesting when we consider autoimmune disease.

Why Your Immune System Needs Cortisol

We often hear that cortisol is bad for our health, but the reality is that we couldn’t function without it.

Cortisol is produced by our adrenal glands and helps regulate everything from our energy levels and blood sugar to our blood pressure and immune system.

It naturally rises in the morning to help us wake up and gradually falls throughout the day. It also increases when we’re under stress, whether that’s because we’re rushing to meet a deadline, recovering from an infection or dealing with something emotionally difficult.

And while we tend to think of this as a negative response, it’s actually an important part of how our body protects us.

One of cortisol’s jobs is to help keep inflammation under control.

Inflammation isn’t necessarily a bad thing. If you cut your finger or develop an infection, your immune system needs to respond. It sends immune cells to the affected area, helping protect you and begin the repair process.

But once that job is done, the inflammatory response needs to settle down. Cortisol is one of the signals that helps make this happen.

It helps prevent the immune system from remaining unnecessarily active, which is particularly important when we’re talking about autoimmune conditions, where the immune system mistakenly targets our own tissues.

So rather than thinking of cortisol as something we should always be trying to lower, we need to understand why it’s there in the first place.

What Happens When Inflammation Doesn’t Settle Down?

Something I find fascinating about the immune system is how carefully it needs to balance protecting us from harm with preventing unnecessary damage.

We have immune cells that encourage inflammation when it’s needed, alongside others that help keep the response under control.

For example, some immune cells help protect us against infections in areas such as the gut and skin. But when their activity becomes excessive, they can contribute to the inflammation associated with conditions such as psoriasis and rheumatoid arthritis.

Other immune cells help prevent our immune system from mistakenly attacking healthy tissue. Cortisol plays a role in regulating this balance.

What’s particularly interesting is that the immune system and the systems controlling cortisol are constantly communicating with one another.

When inflammation increases, our immune system sends signals to the brain, which can encourage the body to produce more cortisol. This helps prevent inflammation from becoming excessive.

Under normal circumstances, this works rather well. But what happens when inflammation continues for months or years?

Research suggests that ongoing inflammation can sometimes change the way our body regulates cortisol. And when that happens, it may become more difficult to keep inflammatory responses under control.

This can contribute to a cycle where inflammation influences cortisol regulation, while changes in cortisol activity may make it harder for the body to manage that inflammation.

It’s one of the reasons chronic inflammation can be so complicated.

Can Chronic Stress Lead to Low Cortisol?

This is something I think is often misunderstood. When we experience stress, our body generally responds by producing more cortisol. This helps us meet the additional demands we’re facing.

But when stress continues over a long period, the response isn’t always so straightforward.

Our brain and adrenal glands communicate constantly to regulate cortisol production. Researchers have found that prolonged stress and chronic inflammation can sometimes affect this communication.

For some people, cortisol levels may remain elevated. For others, the normal daily pattern may change, or the body may produce less cortisol than we might expect in response to the inflammation present.

This doesn’t mean that everyone experiencing chronic stress will develop low cortisol. And it certainly doesn’t mean that feeling exhausted is proof that your adrenal glands have stopped working.

What it does tell us is that prolonged stress can influence the way our body manages cortisol, and that response can vary considerably between individuals. This is particularly relevant when someone is already living with an inflammatory or autoimmune condition.

Their immune system may be producing inflammatory signals over a prolonged period, while the illness itself may also be affecting their sleep, energy, recovery and ability to cope with everyday demands.

It’s a relationship that works in both directions.

Why Some People Have Autoantibodies but No Autoimmune Symptoms

Another interesting area of autoimmune research is why some people develop autoantibodies but never go on to develop an autoimmune disease.

Autoantibodies are proteins produced by the immune system that recognise parts of our own body. For example, someone might have a positive ANA blood test, which can be associated with certain autoimmune conditions, but have no symptoms and never develop the disease.

In other cases, autoantibodies can be present years before someone develops symptoms.

So what makes the difference?

We don’t have all the answers, but we know that autoimmune disease involves more than the presence of antibodies alone.

Genetic susceptibility, infections, hormonal changes and the way the immune system is regulated can all influence whether an autoimmune response develops into an active disease.

And this is where cortisol becomes interesting. Because cortisol helps control inflammation, it is one of the many factors influencing the environment in which our immune cells operate.

It doesn’t simply switch autoimmune disease on or off. But changes in the body’s ability to regulate inflammation may influence how strongly certain immune responses develop.

I think this is an important distinction, particularly for people who have been told they have positive autoantibodies but don’t yet have a clear diagnosis.

A blood test is one piece of information. Understanding what’s happening in the wider body is just as important.

What If Your Body Stops Responding to Cortisol Properly?

This is probably one of the most interesting parts of the research for me. We’ve talked about how cortisol helps control inflammation, but what if the body is producing cortisol and the immune system isn’t responding to it as effectively as it should?

Researchers call this glucocorticoid resistance. Normally, cortisol sends signals to immune cells that help reduce certain inflammatory responses.

But sometimes, particularly when inflammation has been present for a long time, those cells can become less sensitive to the signals.

It’s a little like trying to have a conversation with someone in a noisy room. You’re still speaking, but they’re finding it harder to hear you. The cortisol is still there, but some immune cells may not respond to it as strongly.

Researchers have investigated this in several inflammatory conditions, including rheumatoid arthritis and inflammatory bowel disease.

This doesn’t mean everyone with an autoimmune condition has cortisol resistance, and it’s not something we can identify from symptoms alone. But it does help explain why looking at cortisol levels in isolation doesn’t always give us the full picture.

It’s possible to have cortisol levels within the normal range while inflammation remains elevated.

That doesn’t prove cortisol resistance is present, but it reminds us that measuring how much of a hormone is circulating isn’t necessarily the same as understanding how effectively the body is responding to it.

Why Living With Autoimmune Disease Can Add to the Stress Response

Something I think we need to acknowledge more often is that having an autoimmune condition can itself be stressful. If you’re dealing with pain, fatigue, digestive problems, hair loss or unpredictable flare-ups, it can affect almost every part of your life.

You might find yourself worrying about whether you’ll have enough energy to get through the day, whether your symptoms will worsen or whether you’ll be able to make plans without having to cancel them.

And then there’s the frustration of trying to find answers, particularly if you’ve spent years feeling that your symptoms haven’t been fully understood. These experiences can place additional demands on the systems involved in our stress response.

At the same time, the inflammation associated with autoimmune disease may also influence those systems.

So the relationship isn’t simply that stress causes inflammation. Inflammation and illness can also contribute to the stress our bodies experience.I think this matters because I never want someone living with autoimmune disease to feel that they’ve caused their condition by not managing stress well enough.

Autoimmune disease is complicated, and stress is only one of many factors that may be involved.

But recognising how closely these systems are connected can help us understand why supporting sleep, recovery and our ability to cope with stress may be valuable alongside other aspects of autoimmune care.

Should You Have Your Cortisol Tested?

Given everything we’ve discussed, you might be wondering whether you should have your cortisol levels checked.

There are certainly circumstances where cortisol testing is important, particularly when a doctor suspects a condition affecting adrenal hormone production.

However, cortisol naturally changes throughout the day, and a single result doesn’t necessarily tell us how the hormone is behaving over time. It also doesn’t tell us how sensitive our immune cells are to cortisol.

This is why I don’t think we should automatically assume that someone experiencing fatigue, poor sleep or ongoing inflammation has a cortisol problem. Those symptoms can have many possible causes, and the most useful investigations will depend on the individual’s circumstances.

When I’m working with someone, I’m interested in understanding their symptoms, health history, sleep, stress, medical treatment and any relevant test results.

The aim is to understand what may be contributing to their current health rather than focusing on one hormone in isolation.

What This Means When I’m Working With Clients

One of the things I’ve learnt through my own experience and clinical practice is that two people with the same autoimmune diagnosis can have very different factors contributing to their symptoms.

For one person, prolonged stress and poor recovery may be particularly important. They might notice that their symptoms become worse following demanding periods at work, disrupted sleep or significant life events.

For someone else, the more relevant factors might include an infection, hormonal changes, nutritional deficiencies or an underlying digestive problem. And often, several factors are involved.

This is why my approach begins with understanding their story and looking at how their symptoms and health history may be connected.

I’m interested in identifying which areas are most likely to make a meaningful difference, rather than recommending the same approach to everyone with an autoimmune condition.

Sometimes that means prioritising sleep and recovery. Sometimes it means investigating nutritional deficiencies, digestive symptoms or other potential contributors. And sometimes it means making sure an existing medical condition is being appropriately assessed and managed.

Whatever the starting point, supporting the body’s ability to regulate inflammation remains an important consideration. That doesn’t mean trying to eliminate inflammation altogether. We need it to protect us from infections and repair damaged tissues.

It’s about understanding what may be contributing to inflammation that continues longer than it should, and identifying appropriate ways to address those factors.

For some clients, stress and recovery may be a particularly important part of that picture. For others, they may be secondary to something else. The skill is in understanding where to focus first.

Looking at Cortisol Differently

I think we’ve become so accustomed to hearing about the negative effects of cortisol that we sometimes forget how important it is for our health. We need cortisol to help us wake up, maintain our blood pressure, respond to illness and regulate inflammation.

And while prolonged stress can affect how our body produces and responds to it, that doesn’t mean cortisol itself is the problem.

For me, the most interesting part of this research is the reminder that our immune system, hormones and nervous system don’t operate independently. They’re constantly communicating, adapting and responding to what’s happening within the body.

And when someone is living with autoimmune disease, understanding those connections may help us make more informed decisions about where to focus our attention.

Rather than asking whether cortisol is simply too high or too low, perhaps a more useful question is how well the systems responsible for regulating inflammation are working together.

Because when it comes to autoimmune health, understanding those relationships can be far more valuable than looking at any single result.

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Frequently Asked Questions

Can chronic stress cause autoimmune disease?

Chronic stress may influence immune regulation and inflammatory signalling, but autoimmune diseases develop through complex interactions involving genetic susceptibility, immune mechanisms and environmental factors. Stress alone cannot reliably explain why someone develops an autoimmune condition.

Can autoimmune inflammation cause low cortisol?

Some chronic inflammatory conditions are associated with altered HPA-axis activity or a cortisol response that appears inadequate relative to the degree of inflammation. However, this doesn’t mean everyone with autoimmune disease has low cortisol, and cortisol patterns vary considerably.

What is glucocorticoid resistance?

Glucocorticoid resistance occurs when cells become less responsive to the effects of glucocorticoid hormones such as cortisol. This can reduce their normal anti-inflammatory effects and has been investigated in several chronic inflammatory conditions.

Can you have normal cortisol levels but still experience inflammation?

Yes. Cortisol concentration is only one factor influencing inflammatory activity. Immune cell responsiveness, inflammatory cytokines, disease activity and many other biological processes also matter. A normal cortisol result does not exclude autoimmune or inflammatory disease.

Should people with autoimmune disease have their cortisol tested?

Not routinely on the basis of an autoimmune diagnosis alone. Cortisol testing may be appropriate when symptoms, examination findings or medical history suggest an adrenal or other endocrine disorder. The choice and timing of testing should be guided by the clinical question.

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About the Author

VJ Hamilton is an award-winning Registered Nutritionist and Functional Medicine Certified Professional with a BSc (Hons) in Biochemistry & Immunology. She is the founder of Autoimmune Health Clinic and specialises in nutritional approaches to autoimmune and inflammatory conditions, combining her scientific background, personal experience of autoimmune illness and clinical practice.

References

1. Knezevic E, Nenic K, Milanovic V, Knezevic NN. The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders. Cells. 2023;12(23):2726. https://doi.org/10.3390/cells12232726
2. Alotiby A. Immunology of Stress: A Review Article. Journal of Clinical Medicine. 2024;13(21):6394. https://doi.org/10.3390/jcm13216394
3. Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. The Lancet. 2009;373(9678):1905–1917. https://doi.org/10.1016/S0140-6736(09)60326-3
4. Nunez SG, Rabelo SP, Subotic N, Caruso JW, Knezevic NN. Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation. International Journal of Molecular Sciences. 2025;26(20):9994. https://doi.org/10.3390/ijms26209994

This article is for educational purposes and is not intended to replace individual medical advice, diagnosis or treatment.