MECHANISM OF SUPPRESSED NEUTROPHIL MOBILIZATION IN A MOUSE MODEL FOR BINGE DRINKING - ROLE OF GLUCOCORTICOIDS

The goals of this study were to determine if suppression of neutrophil accumulation and TNF-alpha production in the peritoneal cavity occurs in mice exposed to a chemical stressor [ethanol (EtOH)], to evaluate the role of EtOH-induced increases in endogenous glucocorticoids in an y such suppression, and to determine if decreased tumor necrosis facto r-alpha (TNF-alpha) production is responsible for decreases in neutrop hil accumulation in EtOH-treated mice. An inflammatory response induce d in the peritoneal cavity of mice by administration of heat-killed Pr opionibacterium acnes (P. acnes) was suppressed by a single dose of Et OH given 1 h before administration of the bacteria, as indicated by de creased accumulation of neutrophils in the peritoneal cavity. The conc entration of TNF-alpha in the peritoneal cavity was also decreased by EtOH, but exogenous TNF-cu did not prevent the suppression of neutroph il accumulation. The glucocorticoid antagonist RU-486 did not prevent the suppression of neutrophil accumulation in mice treated with EtOH, but RU-486 did block suppression of neutrophil accumulation caused by administration of exogenous corticosterone. The suppression of neutrop hil accumulation caused by exogenous corticosterone was less than prod uced by EtOH. These observations suggest that the increase in endogeno us corticosterone induced by EtOH may explain some of the suppression of neutrophil accumulation, but other neuroendocrine mediators (or EtO H per se) are sufficient to cause the full suppressive effect when the action of corticosterone is blocked by RU-486. The results also demon strate that EtOH decreases TNF-cr production, but this is not the mech anism by which neutrophil accumulation is decreased in this model.