Effect of interleukin-1 on ACTH and corticosterone secretion in dexamethasone and adrenalectomized pretreated male rats.

The present study was designed to investigate the role of glucocorticoids in mediating the stimulatory effect of interleukin-1 (IL-1) upon the adrenocortical (AC) axis. Intact male rats were injected with either vehicle or dexamethasone (DEX) (5-50 micrograms/100 g b.w.) and were subsequently exposed to ether stress or to an intracerebroventricular (i.c.v.) injection of 2 U recombinant human IL-1 beta. In addition, adrenalectomized (ADX) rats were injected i.c.v. with 2U IL-1; for comparison ADX rats were also exposed to ether stress and insulin-induced hypoglycemia. In intact rats, ether-stress-induced AC activation was much more sensitive to the DEX inhibitory effect than the IL-1-induced AC activation. In ADX animals, insulin-induced hypoglycemia and ether stress produced a significant increase in ACTH serum values whereas IL-1 administration failed to activate ACTH secretion. Glucocorticoid binding studies showed that an i.c.v. injection of 2 U IL-1, 3 h before sacrifice, markedly reduced the specific in vitro binding of 3H-corticosterone by the nuclear fraction of dorsal hippocampal tissue slices. These results suggest that IL-1 may activate the AC axis, at least in part, by interfering with the negative feedback effect of circulating glucocorticoids.