EFFECTS OF SELECTIVE TYPE-I AND TYPE-II ADRENAL-STEROID AGONISTS ON IMMUNE CELL DISTRIBUTION

Adrenal steroids exert their effects through two distinct adrenal ster oid 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 cel ls and tissues, few data exist on the relative effects mediated throug h these two receptor subtypes. Accordingly, we administered selective type I and II adrenal steroid receptor agonists to young adult male Sp rague-Dawley rats for 7 days and then measured immune cell distributio n in the peripheral blood and spleen. Results were compared with those of similar studies using the naturally occurring glucocorticoid of th e rat, corticosterone, which binds both type I and II receptors. The m ajority of the well characterized effects of adrenal steroids on perip heral blood immune cells (increased neutrophils and decreased lymphocy tes and monocytes) were reproduced by the type II receptor agonist, RU 28362. RU28362 decreased the numbers of all lymphocyte subsets [T-cell s, B-cells, and natural killer (NK) cells] to very low absolute levels . The largest relative decrease (i.e. in percentage) was seen in B-cel ls, whereas NK cells exhibited the least relative decrease and actuall y showed a 2-fold increase in relative percentage during RU28362 treat ment. Similar to RU28362, the type I receptor agonist, aldosterone, si gnificantly reduced the number of lymphocytes and monocytes. In contra st to RU28362, however, aldosterone significantly decreased the number of neutrophils. Moreover, aldosterone decreased the number of T-helpe r cells and NK cells, while having no effect on the number of B-cells or T-suppressor/cytotoxic cells. Corticosterone at physiologically rel evant concentrations had potent effects on immune cell distribution, w hich were indistinguishable from those of the type II receptor agonist , RU28362. Taken together, these results indicate that effects of adre nal steroids on immune cell distribution are dependent on the receptor subtype involved as well as the specific cell type targeted. These fa ctors allow for varied and complex effects of adrenal steroids on the immune system under physiological conditions.