Acute interactions between cytokines and alcohol on ACTH and corticosterone secretion in the rat.
Possible interactions between alcohol (EtOH) and interleukins (ILs) were studied in intact and adrenalectomized (ADX) rats. In intact animals, administration of 0.3 or 0.65 g EtOH/kg 30 min to 4 hr earlier did not cause measurable changes in plasma adrenocorticotropic hormone (ACTH) levels measured immediately before acute intravenous injection of IL-1 beta or endotoxin [lipopolysaccharide (LPS)], and did not interfere with the ability of either treatments to increase ACTH secretion. Administration of 1.5 g EtOH/kg, on the other hand, resulted in elevated plasma ACTH and corticosterone 30 min later, and significantly decreased the magnitude of the ACTH response to IL-1 beta in both intact and ADX rats. When administered 4 hr before the cytokine, however, 1.5 g EtOH/kg did not alter the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to IL-1 beta. Studies of the reverse paradigm were conducted in rats injected with LPS, a means of increasing endogenous IL-1 levels. Intraperitoneal administration of alcohol 4 hr later resulted in measurably blunted ACTH release by intact rats, but not ADX animals. We conclude that when prior alcohol administration does not result in elevated ACTH levels at the time of IL-1 injection, no alteration in the HPA axis' response to the cytokine is observed. As we have shown in other experiments that circulating levels of corticosterone were temporarily increased by all doses of alcohol used in the present study, these results suggest that steroid feedback did not play a major role in modulating the ability of IL-1 beta to activate the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)
Rivier
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Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007375:Interleukin-1; D007378:Interleukins; D008070:Lipopolysaccharides; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone