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This post is by guest blogger Matthew Savage 

In the most recent decade, research into our endocrine system has grown dramatically, helping us understand the importance of the endocrine system to our overall health and how it contributes to the health of our whole body through its interaction with other systems. Psychoneuroimmunology is the study which developed from this interest, looking closely at the interaction of the central nervous system, the immune system and the endocrine system. Previously, it was assumed that the immune system was solely responsible for protection against illness, and fighting off infections and diseases. However, it is now widely accepted that the brain communicates with the immune system through the autonomic nervous system and also through neuroendocrine activity (Ader, 2001). Each system may be processing information alongside each other, making decisions independently but also interacting with each other constantly. For example, a cognitive event is not separate from an endocrine or an immunological event but a complex, multi-directional interaction of all three systems.

So why is this important to understand?

A cognitive event, such as a depressive episode, is caused by a mixture of hormones and a link between stress and immunity. Stressor exposure and immune response were an early topic of interest in psychoneuroimmunology (PNI) and evidence supports the link that psychological and physical stressor exposure can affect the immune system (Nes and Segerstrom, 2004). More than 300 studies support this link, looking at both acute stressors (which only last a few minutes) to chronic stressors (which last for days and even years). During periods of acute stress or “threat” as our body perceives it, our sympathetic nervous system responds by releasing the hormones epinephrine and norepinephrine, leading to raised heart rate and increased blood pressure, allowing our body to prepare for “flight or fight”. Whilst this occurs, our endocrine system will also respond, changing levels of hormones such as cortisol, a steroid hormone produced by the hypothalamic–pituitary–adrenal (HPA) axis and this can then affect our immune system, such as increase antibodies in our saliva and increased production of cytokines that stimulate nonspecific immunity. All of these actions are beneficial to the body in the short term but become problematic over a long period of time. Chronic stressors decrease cytotoxic and antibody-producing functions of immune cells, making us more susceptible to illness and infection. Chronic stress can cause dysregulation of the immune response because of changes in blood chemistry and these can cause errors, including identifying part of the body as foreign and producing a response to this. Dysregulation increases the probability of the immune system making errors, and when this occurs over a long period of time, dysregulation becomes learnt, and our body may develop chronic conditions and allergies as chronic stress can damage immune tissue. Allergies to gluten or pollen, gut conditions such as Irritable Bowel Syndrome or autoimmune conditions such as Multiple Sclerosis can all develop from high levels of stress hormones over an extended period of time and due to the damage they cause to our immune system. Because psychoneuroimmunology covers a broad area of scientific research, ranging from the molecular to the interpersonal, it provides a real opportunity to build a more comprehensive model of health, particularly in the process of disease prevention and stress managements (Daruna, 2012).

Psychoneuroimmunology and experimental data

A number of very interesting studies have provided strong evidence for the links between the systems discussed. An excellent experiment took place in 2010, which looked at the link between Depression, Cortisol and Interleukin-6 (IL-6), a pro-inflammatory cytokine which is considered to be one of the most important cytokines which help to fight viral infections, such as COVID-19. Donovan et al (2010) took a number of measures in a clinically anxious experimental group and non-anxious control group. It was found that anxious participants had significantly lower levels of morning cortisol levels and higher levels of IL-6 in circulation. Whilst at first, lower levels of the hormone cortisol may seem a good thing to have, it is vital in the morning to wake us up and prepare our body for the day. In addition to this, increased levels of IL-6 can lead to damage of the arteries and dysregulation of this cytokine is implicated in the onset and development of several disease states, particularly autoimmune and chronic inflammatory diseases. These findings are important as they suggest that those with anxiety may be at risk for inflammatory diseases such as Rheumatoid Arthritis.

Another very interesting study by Antoni et al (2009) involved looking at how Cognitive Behavioural Stress Management (CBSM) in women affected the brain, behaviour and immunity of women with breast cancer. The study examined 128 women with stages 1-3 breast cancer who were recruited 4-8 weeks after surgery. The experiment compared two groups, one of which undertook 10 weeks of group based cognitive behavioural stress management (CBSM) intervention and a second control group which had a 1-day psycho-educational group session. Questionnaires and late afternoon blood samples at study entry and 6 and 12 months after assignment were taken. Results found that those in the group-based cognitive behavioural stress management had better psychosocial adaption and physiological adaption, with lower cortisol levels, greater Th1 cytokine production compared to the control group. These effects appeared to hold across the entire 12-month period of observation, suggesting that the CBSM group helped to reduce dysregulation of the neuro-endocrine system following cancer treatment. This is an important finding as it suggests that behavioral interventions that address dysregulated neuro-endocrine function could play a clinically significant role in optimizing host immunologic resistance during a vulnerable period. Stress management could be utilized as a low-cost treatment to improve outcomes of cancer patients following stressful treatments.

Psychoneuroimmunology is also helping us to understand individual stress management

Different people handle stress exposure in different ways, and it is important to consider this in disease prevention. Reactivity is a stable trait that predicts an individual’s level of physiological reaction to a stressor or psychological state. If a person is stress reactive, they have a low threshold for threat, meaning the stress response is called upon regularly. As the stress response occurs, it moves blood away from the neocortex, reducing individual empathy and compassion and, over a longer period of time, can lead to generalized anxiety disorders and depression, particularly if stress reactivity is developed during childhood or following trauma. In addition to this, it has been suggested that women who suffered from breast cancer were twelve times more likely to have experienced trauma and have higher stress reactivity across the lifespan (Chen, 1995, 2003). Despite this example, it is still being heavily debated (Protheroe, 1999, 2002), however it is now widely accepted that our reactivity is a risk factor for multiple chronic illnesses and continues to be a real focus of psychoneuroimmunology.


There is a lot of strong evidence which suggest this complex interaction between the psychological, endocrine and immunological systems and lots of experimental data linking chronic stress, including our levels of reactivity, to disease states. Chronic exposure to stress hormones damages the immune tissues and these can lead to further damage in a vicious circle. This will reduce our ability to fight infection and produce immune response and that is why the endocrine system is so important. These are important connections to understand and further developments in the field of psychoneuroimmunology may help us to develop better interventions, particularly in reducing stress and anxiety which can change immune function sufficiently to be clinically relevant. Providing more successful outcomes for better disease prevention and recovery will remain a strong focus of psychoneuroimmunology.

About Matt Savage

Matthew Savage has an MSc in Psychology, is a qualified personal trainer, and has worked within the field of cognitive rehabilitation for 5 years. He is an FA qualified football coach, with a keen interest in moral behaviour and wellbeing within team sports. 


Ader, R (2001) International Encyclopedia of the Social & Behavioral Sciences

Antoni et al (2009) Cognitive Behavioural Stress Management in women with breast cancer. Journal: Brain, Behavior, and Immunity

Daruna, H, (2012). Introduction to Psychoneuroimmunology (Second Edition)

Donovan, A et al (2010) Depression, Cortisol and Interleukin-6

Nes L.S, Segerstrom, S.C, (2017). Reference Module in Neuroscience and Biobehavioural Psychology

Nervous system


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