Review
Stress hormones and immune function

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Abstract

Over the past 20 years we have demonstrated both in animal models and in human studies that stress increases neuroendocrine hormones, particularly glucocorticoids and catecholamines but to some extent also prolactin, growth hormone and nerve growth factor. We have also shown that stress, through the action of these stress hormones, has detrimental effects on immune function, including reduced NK cell activity, lymphocyte populations, lymphocyte proliferation, antibody production and reactivation of latent viral infections. Such effects on the immune system have severe consequences on health which include, but are not limited to, delayed wound healing, impaired responses to vaccination and development and progression of cancer. These data provide scientific evidence of the effects of stress on immune function and implications for health.

Introduction

For many years it has been known that stress is detrimental to health. In 1974 Hans Seyle defined stress as “the non-specific response of the body to any demand imposed upon it”[1]. This definition of stress was later modified in 1992 by Chrousos and Gold and the term “non-specific” replaced by the hypothesis that above a threshold intensity any stressor would elicit the “stress syndrome”[2]. Stress can occur in a variety of forms, physical or psychological, acute or chronic. It is possible and probable that different forms of stress will have different effects on the stress hormones released and on immune function. Stress is known to cause the release of several stress hormones—primarily glucocorticoids though activation of the hypothalamic–pituitary–adrenal (HPA) axis and catecholamines through the sympathetic nervous system. For over two decades we have investigated the effects of various forms of stress, both in human studies and in animal models, on neuroendocrine hormones and on cellular aspects of both the innate and adaptive immune responses. The findings of these studies are reviewed here.

Section snippets

Models of stress

Over the years we have used numerous models of stress in our studies. In human subjects these have included laboratory-induced stressors such as a speech stress test and mental arithmetic stress test [3], life stressors such as medical students undergoing examination stress, marital stress, physical training stress in West Point Cadets, caregivers of Alzheimer’s or dementia patients, breast cancer patients, pain following surgery, and psychological stressors such as feelings of loneliness,

Neuroendocrine responses to stress

Stress, both physical and psychological, results in neuroendocrine signals being released from the brain that can affect immune function. The main two neuroendocrine pathways activated in response to stress that control the immune system are the HPA axis which results in release of glucocorticoids, and the sympathetic nervous system which results in release of catecholamines, epinephrine and norepinephrine. However, there are other neuroendocrine factors that are released following stress that

Effect of stress on immune function

Stress has been shown to have detrimental effects on the immune system. These include changes in lymphocytes populations, in the ratio of helper:suppressor T cells, decreased lymphocyte proliferation, NK cell number and activity, impaired antibody responses and reactivation of latent viral infections (Fig. 2).

Implications for health

The effects of stress hormones on immune function described above have numerous implications for health. Three of these—vaccination, cancer and wound healing—are discussed below (Fig. 3).

Conclusion

Stress, through the actions of stress hormones, has many detrimental effects on immune function which in turn have implications for health. Interestingly, the use of relaxation techniques has been shown to reverse some of these deleterious effects on immune function. Thus, the role of stress in disease, and the usefulness of practices that reduce stress should not be underestimated.

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