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.
Weidenfeld
J
J
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Abramsky
O
O
Ovadia
H
H
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004986:Ether; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013312:Stress, Physiological / Q000139:chemically induced / Q000503:physiopathology
D007375:Interleukin-1; D011994:Recombinant Proteins; D004986:Ether; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone