Effect of Acute Alcohol Treatment on the Release of ACTH, Corticosterone, and Pro‐Inflammatory Cytokines in Response to Endotoxin

Abstract

This study investigated the effects of acute alcohol pretreatment on endotoxin lipopolysaccharide (LPS)-induced release of ACTH, corticosterone, and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in plasma and at various tissues sites. Specifically, we wanted to determine whether alcohol pretreatment would alter the ACTH, corticosterone, and cytokine responses to LPS, and whether the alcohol-induced changes in ACTH/corticosterone secretory rates of endotoxemic rats were accompanied by similar changes in cytokine production. Alcohol, 3.0 g/kg, intragastric (i.g.), was administered 3 hr before LPS treatment [1.0 or 5.0 microg/kg, intravenous (i.v.)], and ACTH, corticosterone, and cytokines levels were measured over a 4 hr post LPS treatment. In intact rats, the alcohol-induced plasma ACTH and corticosterone responses had returned to basal levels by the time of LPS injection, and alcohol pretreatment increased the corticosterone but not the ACTH response after LPS treatment. In contrast, in adrenalectomized 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 phenomenon 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, adrenal glands, and spleen, and that these responses were not altered by alcohol pretreatment. On the basis of these results, we concluded that acute alcohol treatment increased LPS-induced corticosterone response, while it blunted the IL-6 response. LPS also significantly elevated pituitary, adrenal, and splenic contents of TNF-alpha and IL-6, and alcohol did not influence these changes.