AJP - Endocrinology and Metabolism, Vol 265, Issue 6 E825-E830, Copyright © 1993 by American Physiological Society
Differential effects of corticosteroids on rat peripheral blood T-lymphocyte mitogenesis in vivo and in vitro
G. J. Wiegers, G. Croiset, J. M. Reul, F. Holsboer and E. R. de Kloet
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
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.
