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 hypothalamicpituitary‐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‐1 β (IL‐1β) 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‐a 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‐1β (400 ng/kg) or LPS (1 μg/kg), both injected intravenously 7 days later, to release ACTH. Drug pretreatment did not significantly alter the tumor necrosis factor‐α 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 (1L‐1β 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.