Mechanism of suppressed neutrophil mobilization in a mouse model for binge drinking: role of glucocorticoids

Abstract

The goals of this study were to determine if suppression of neutrophil accumulation and TNF-α 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 any such suppression, and to determine if decreased tumor necrosis factor-α (TNF-α) production is responsible for decreases in neutrophil accumulation in EtOH-treated mice. An inflammatory response induced in the peritoneal cavity of mice by administration of heat-killed Propionibacterium acnes ( P. acnes) was suppressed by a single dose of EtOH given 1 h before administration of the bacteria, as indicated by decreased accumulation of neutrophils in the peritoneal cavity. The concentration of TNF-α in the peritoneal cavity was also decreased by EtOH, but exogenous TNF-α did not prevent the suppression of neutrophil 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 neutrophil accumulation caused by exogenous corticosterone was less than produced by EtOH. These observations suggest that the increase in endogenous corticosterone induced by EtOH may explain some of the suppression of neutrophil accumulation, but other neuroendocrine mediators (or EtOH per se) are sufficient to cause the full suppressive effect when the action of corticosterone is blocked by RU-486. The results also demonstrate that EtOH decreases TNF-α production, but this is not the mechanism by which neutrophil accumulation is decreased in this model.