Effects of selective type I and II adrenal steroid agonists on immune cell distribution.
Adrenal steroids exert their effects through two distinct adrenal steroid receptor subtypes; the high affinity type I, or mineralocorticoid, receptor and the lower affinity type II, or glucocorticoid, receptor. Adrenal steroids have well known effects on immune cell distribution, and although both type I and II receptors are expressed in immune cells and tissues, few data exist on the relative effects mediated through these two receptor subtypes. Accordingly, we administered selective type I and II adrenal steroid receptor agonists to young adult male Sprague-Dawley rats for 7 days and then measured immune cell distribution in the peripheral blood and spleen. Results were compared with those of similar studies using the naturally occurring glucocorticoid of the rat, corticosterone, which binds both type I and II receptors. The majority of the well characterized effects of adrenal steroids on peripheral blood immune cells (increased neutrophils and decreased lymphocytes and monocytes) were reproduced by the type II receptor agonist, RU28362. RU28362 decreased the numbers of all lymphocyte subsets [T-cells, B-cells, and natural killer (NK) cells] to very low absolute levels. The largest relative decrease (i.e. in percentage) was seen in B-cells, whereas NK cells exhibited the least relative decrease and actually showed a 2-fold increase in relative percentage during RU28362 treatment. Similar to RU28362, the type I receptor agonist, aldosterone, significantly reduced the number of lymphocytes and monocytes. In contrast to RU28362, however, aldosterone significantly decreased the number of neutrophils. Moreover, aldosterone decreased the number of T-helper cells and NK cells, while having no effect on the number of B-cells or T-suppressor/cytotoxic cells. Corticosterone at physiologically relevant concentrations had potent effects on immune cell distribution, which were indistinguishable from those of the type II receptor agonist, RU28362. Taken together, these results indicate that effects of adrenal steroids on immune cell distribution are dependent on the receptor subtype involved as well as the specific cell type targeted. These factors allow for varied and complex effects of adrenal steroids on the immune system under physiological conditions.
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
A H
AH
Miller
R L
RL
Spencer
J
J
hassett
C
C
Kim
R
R
Rhee
D
D
Ciurea
F
F
Dhabhar
B
B
McEwen
M
M
Stein
D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D000732:Androstanols; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003345:Corticosterone