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 in duced a significant and long-lasting blunting of the hypothalamic-pitu itary-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 presenc e of a phenomenon of selective neuroendocrine tolerance. To further te st this hypothesis, we determined whether an initial alcohol challenge would alter the ACTH response to immune signals, such as interleukin- 1 beta (IL-1 beta) and/or endotoxin (lipopolysaccharide; LPS). Because of the functional connection between the HPA axis and immune response s, we also determined whether the LPS-induced release of tumor necrosi s factor-alpha and interleukin-6, as well as IgG and IgM responses to an antigenic challenge, would be influenced by previous exposure to al cohol. We show here that the intragastric injection of 3 g of alcohol/ ky daily for 3 days did not significantly alter the ability of IL-1 be ta (400 ng/kg) or LPS (1 mu g/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 interl eukin-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 indi cate that an initial exposure to alcohol does not induce long-term cha nges in the ability of an immune signal (IL-1 beta or endotoxin) to ac tivate the HPA axis. In contrast, a small but detectable enhancement o f cytokine responses to LPS, and of the IgG response to phosphocholine -keyhole limpet hemocyanin, was observed.