Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones.
The numbers and proportions of leukocytes in the blood provide an important representation of the state of activation of the immune system, and of the pattern of distribution of immune cells in the body. We have shown previously that acute stress induces large, rapid, and reversible changes in the distribution of peripheral blood leukocyte subpopulations in the rat. The studies described here specifically investigate the role played by adrenal steroid hormones in mediating stress-induced changes in blood leukocyte distribution. Since adrenal steroids act at two distinct receptor subtypes that show a heterogeneity of expression in immune cells and tissues, the role played by each subtype in mediating changes in leukocyte distribution is also investigated. Cyanoketone, a corticosterone (CORT) synthesis inhibitor, significantly reduced the decrease in lymphocyte numbers observed during stress and significantly enhanced the increase in neutrophil numbers observed after the cessation of stress. Acute administration of aldosterone (a specific type I adrenal steroid receptor agonist) to adrenalectomized animals did not have a significant effect on blood leukocyte numbers. In contrast, acute administration of CORT (the endogenous type I and type II receptor agonist), or RU28362 (a specific type II receptor agonist), to adrenalectomized animals produced changes in leukocyte distribution that were similar to those observed in intact animals during stress. These results suggest that CORT, acting at the type II adrenal steroid receptor, is a major mediator of the stress-induced changes in blood lymphocyte and monocyte distribution.
Dhabhar
F S
FS
Rockefeller University, New York, NY 10021, USA.
Miller
A H
AH
McEwen
B S
BS
Spencer
R L
RL
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000302:Adrenal Cortex / Q000503:physiopathology*; D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D003489:Cyanoketone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007958:Leukocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000097:blood / Q000276:immunology* / Q000503:physiopathology
D000305:Adrenal Cortex Hormones; D004791:Enzyme Inhibitors; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003489:Cyanoketone; D000450:Aldosterone; D015096:3-Hydroxysteroid Dehydrogenases; D003345:Corticosterone