Differential effects of corticosteroids on rat peripheral blood T-lymphocyte mitogenesis in vivo and in vitro.
The effects of corticosteroids were studied on the concanavalin A (Con A)-induced mitogenesis of peripheral blood T-lymphocytes obtained from intact and adrenalectomized (ADX) Wistar rats. One week of adrenalectomy reduced the proliferative response of T-cells by 65% compared with sham-operated controls. Substitution of ADX rats with subcutaneously implanted 12.5-mg corticosterone (Cort) pellets, which resulted in low circulating Cort levels (17 +/- 3 nM), restored the reduced proliferative capacity to that of sham-ADX animals. In contrast, T-lymphocyte proliferation was nearly absent in ADX rats substituted with high circulating Cort levels (173 +/- 15 nM; 100-mg Cort pellet). In vitro, Cort suppressed the mitogenic response of T-lymphocytes from ADX and sham-ADX animals. The glucocorticoid antagonist RU-486 (500 nM) completely blocked this suppressive effect. However, a 10 times lower concentration of RU-486 reversed the effects of a low (10 nM) Cort concentration from suppression to stimulation. It is concluded that high Cort concentrations in vivo and in vitro suppressed T-lymphocyte mitogenesis but that low concentrations in vivo were stimulatory, whereas this stimulation in vitro occurred only in the presence of antiglucocorticoids. These opposing effects of Cort emphasize a bimodal regulatory role of this hormone in immune regulation that may be mediated by different corticosteroid receptors.
Wiegers
G J
GJ
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
Croiset
G
G
Reul
J M
JM
Holsboer
F
F
de Kloet
E R
ER
D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D003208:Concanavalin A; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004343:Drug Implants; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D004343:Drug Implants; D003208:Concanavalin A; D015735:Mifepristone; D003345:Corticosterone