Prenatal alcohol exposure blunts interleukin-1-induced ACTH and beta-endorphin secretion by immature rats.
The functional relationship between the immune and the hypothalamic-pituitary-adrenal (HPA) axis [and in particular the release of pro-opiomelanocortin (POMC)-related peptides and corticosteroids induced by interleukins (ILs)] is essential for coordinating the appropriate immune responses to pathogens. Exposure of pregnant mammalian females to alcohol results in abnormal immune functions in the offspring, as well as in altered HPA axis activity. We therefore tested the hypothesis that prenatal alcohol exposure might modify the stimulatory action of ILs on the HPA axis of the pups, thus providing a mechanisms through which this treatment results in increased rate of infectious or inflammatory processes. Pregnant dams were fed a liquid alcohol diet throughout gestation. Dams with free access to food (ad libitum group), or dams fed an isocaloric diet in which sucrose replaced alcohol (pair-feeding), were also included. At 22-24 days of age, the pups were injected intraperitoneally with IL-1 beta, corticotropin-releasing factor (CRF), or the vehicle. Blood samples obtained 1-2 hr later indicated that the alcohol diet resulted in significantly blunted adrenocorticotropic hormone (ACTH) and beta-endorphin, but not corticosterone release, in response to IL-1 beta. Pair-fed pups also showed some decrease in their pituitary response, although to a lesser degree. In contrast, there was no measurable difference in the ability of CRF to increase plasma ACTH levels. These results suggest that prenatal exposure to alcohol interferes with the stimulatory action of IL-1 beta on the secretion of POMC-related peptides, a phenomenon probably not caused by decreased pituitary responsiveness to CRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
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Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Rivier
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C
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004597:Electroshock; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000097:blood*
D007375:Interleukin-1; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone