Effect of acute alcohol treatment on the release of ACTH, corticosterone, and pro-inflammatory cytokines in response to endotoxin

This study investigated the effects of acute alcohol pretreatment on endoto xin lipopolysaccharide (LPS)-induced release of ACTH, corticosterone, and p ro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and inter leukin-6 (IL-6) in plasma and at various tissues sites. Specifically, we wa nted to determine whether alcohol pretreatment would alter the ACTH, cortic osterone, and cytokine responses to LPS, and whether the alcohol-induced ch anges in ACTH/corticosterone secretory rates of endotoxemic rats were accom panied by similar changes in cytokine production. Alcohol, 3.0 g/kg, intrag astric (ig), was administered 3 hr before LPS treatment [1.0 or 5.0 mu g/kg , intravenous (iv)], and ACTH, corticosterone, and cytokines levels were me asured over a 4 hr post LPS treatment. Ln intact rats, the alcohol-induced plasma ACTH and corticosterone responses had returned to basal levels by th e time of LPS injection, and alcohol pretreatment increased the corticoster one but not the ACTH response after LPS treatment. In contrast, in adrenale ctomized corticosterone-replaced animals, the alcohol-induced ACTH response was still elevated at the time of LPS injection. However, the overall ACTH response of rats pretreated with the vehicle or alcohol was statistically similar. As expected, LPS also significantly stimulated both TNF-alpha and IL-6 release into the general circulation. The IL-6, but not the TNF-alpha, response was inhibited by alcohol pretreatment in intact rats, a phenomeno n that was not present in adrenalectomized animals. Finally, we showed that LPS also augmented the TNF-alpha and/or IL-6 content of the pituitary, adr enal glands, and spleen, and that these responses were not altered by alcoh ol pretreatment. On the basis of these results, we concluded that acute alcohol treatment in creased LPS-induced corticosterone response, while it blunted the IL-6 resp onse. LPS also significantly elevated pituitary, adrenal, and splenic conte nts of TNF-alpha and IL-6, and alcohol did not influence these changes.