Viewpoint On

• Selye H. Thymus and adrenals in the response of the organism to injuries and intoxications. Brit J Exper Path. 1936;17:234-248
• Selye H. Studies on adaptation. Endocrinology 1937;21:169-188
• Harlow CM, Selye H. The blood picture in the alarm reaction. Proc Soc Exp Biol Med. 1937;36;141-144

Hans Selye (1907-1982) is the “Founder of Stress Theory” (1). He defined “the general adaptation syndrome”, which is the sum of all non-specific, systemic reactions of the body, which ensue upon long continued exposure to stress. In order to induce stress in rats, he exposed animals to many different nocuous alarm signals such as, e.g., toxins like formaldehyde. He recognized three different phases of the general adaptation syndrome: 1) a short-lived alarm reaction (including shock and counter-shock), 2) resistance, and 3) exhaustion (death). In these studies, he described the non-specific, systemic stress reactions of the body. He looked on body weight, weight of adrenal glands, blood pressure, body temperature, heart rate, blood sugar concentration, blood levels of chloride, histological changes of organs, and many more.

The “immunological idea” of Selye

Although Selye was not an immunologist, he recognized two important aspects after severe stress, which he incorporated into his theory of the general adaptation syndrome:

1. Shrinkage of lymphoid organs such as thymus, spleen, and lymph nodes
2. Increase of neutrophils and decrease of lymhocytes

Many different stress reactions can stimulate both events. Importantly, prior adrenalectomy partly inhibited the effects (Fig. 1). Other authors later added the fact that stress hormones induce immunoglobulin secretion (2) etc.

Figure 1. Stress reactions induce shrinkage of the thymus (and other lymphoid organs, not shown) and a marked increase in blood leukocyte count. Graph created by the blogger combining the tabular data published in the three above-mentioned original works.

Today we recognize that reactions through stress axes such as the sympathetic nervous system and the adrenal glands can stimulate the immune system at early time points during stress. A typical reaction is the mobilization and extravasation of blood immune cells (high monocytes/neutrophils, low lymphocytes). In the long term, stress responses inhibit the immune system, particularly when they are strong.

In one form or the other, stress-stimulated immediate changes of blood immune cells stood the test of time, and some of the experiments have also been published in Neuroimmunomodulation (3-10).

References

1. Tan SY, Yip A. Hans Selye (1907-1982): Founder of the stress theory. Singapore Med J. 2018;59:170-171
2. Dougherty TF, Chase JH, White A. Pituitary-adrenal cortical control of antibody release from lymphocytes. An explanation of the anamnestic response. Proc Soc Exp Biol Med. 1945;58:135-140
3. Tarcic N, Levitan G, Ben-Yosef D, Prous D, Ovadia H, Weiss DW. Restraint stress-induced changes in lymphocyte subsets and the expression of adhesion molecules. Neuroimmunomodulation. 1995;2:249-257
4. Nakata A, Araki S, Tanigawa T, Sakurai S, Yokoyama M. Effects of uncontrollable and controllable electric shocks on T lymphocyte subpopulations in the peripheral blood, spleen, and thymus of rats. Neuroimmunomodulation. 1996;3:336-341
5. Sudo N, Yu XN, Sogawa H, Kubo C. Restraint stress causes tissue-specific changes in the immune cell distribution. Neuroimmunomodulation. 1997;4:113-119
6. Sudo N, Oyama N, Yu XN, Kubo C. Restraint stress-induced elevation of endogenous glucocorticoids decreases Peyer’s patch cell numbers via mechanisms that are either dependent or independent on apoptotic cell death. Neuroimmunomodulation. 2001;9:333-339
7. Kumlien Georén S, Olgart Hoglund C, Tcacencu I, Wikstrom AC, Stierna P. Timing-dependent effects of restraint stress on eosinophilic airway inflammation in mice. Neuroimmunomodulation. 2008;15:157-164
8. Martínez-Carrillo BE, Godinez-Victoria M, Jarillo-Luna A, Oros-Pantoja R, Abarca-Rojano E, Rivera-Aguilar V, Yépez JP, Sánchez-Torres LE, Campos-Rodríguez R. Repeated restraint stress reduces the number of IgA-producing cells in Peyer’s patches. Neuroimmunomodulation. 2011;18:131-141
9. Dhabhar FS. Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation. 2009;16:300-317
10. Haake P, Krueger TH, Goebel MU, Heberling KM, Hartmann U, Schedlowski M. Effects of sexual arousal on lymphocyte subset circulation and cytokine production in man. Neuroimmunomodulation. 2004;11:293-298