Effect of pretreatment with alcohol on subsequent endocrine and immune responses in the adult male rat.
We have previously shown that daily injection of alcohol for 3 days induced a significant and long-lasting blunting of the hypothalamic-pituitary-adrenal (HPA) axis response to a subsequent treatment with this drug. The fact that, in contrast, the HPA axis response to footshocks was not altered by prior alcohol administration, suggested the presence of a phenomenon of selective neuroendocrine tolerance. To further test this hypothesis, we determined whether an initial alcohol challenge would alter the ACTH response to immune signals, such as interleukin-1beta (IL-1beta) and/or endotoxin (lipopolysaccharide; LPS). Because of the functional connection between the HPA axis and immune responses, we also determined whether the LPS-induced release of tumor necrosis factor-alpha and interleukin-6, as well as IgG and IgM responses to an antigenic challenge, would be influenced by previous exposure to alcohol. We show here that the intragastric injection of 3 g of alcohol/kg daily for 3 days did not significantly alter the ability of IL-1beta (400 ng/kg) or LPS (1 microg/kg), both injected intravenously 7 days later, to release ACTH. Drug pretreatment did not significantly alter the tumor necrosis factor-alpha response to the low dose of endotoxin used, whereas there was a tendency toward increased circulating interleukin-6 levels in alcohol-pretreated animals. Finally the IgG, but not IgM, response to the antigen phosphocholine-keyhole limpet hemocyanin was significantly (p < 0.05) augmented in rats administered alcohol 7 days before the antigenic challenge. Collectively, these results indicate that an initial exposure to alcohol does not induce long-term changes in the ability of an immune signal (IL-1beta or endotoxin) to activate the HPA axis. In contrast, a small but detectable enhancement of cytokine responses to LPS, and of the IgG response to phosphocholine-keyhole limpet hemocyanin, was observed.
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The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004731:Endotoxins / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D000324:Adrenocorticotropic Hormone