RU486 Abrogates Ethanol-Induced Apoptosis of Splenic Natural Killer Cells in a Mouse Model of Binge Drinking

Ethanol (EtOH) decreases the number and activity of splenic natural killer (NK) cells in a mouse model of binge drinking. The fate of the lost splenic NK cells is unknown. In the present study, mice were exposed to EtOH in a model designed to represent binge drinking. The percentages of NK cells labeled with NK1.1 antibodies were determined by flow cytometry. The results demonstrated that EtOH decreases splenic NK cell percentages. In addition, EtOH suppresses NK cell percentages in peripheral blood-, bone marrow- and peritoneal cavity-derived cells. Splenic NK cell apoptosis was evaluated on sub-G1 apoptosis assay. Flow cytometric analysis demonstrated a significant increase in the percentage of apoptotic NK cells in the spleen 3-6 hr after administration of EtOH. This increase was completely blocked by the glucocorticoid antagonist RU486. RU486 also substantially blocked the increased protein expressions of Bax, Bak, cleaved caspase-3, and cleaved caspase-9 induced by EtOH. Collectively, these results indicated that EtOH-induced glucocorticoids induce splenic NK cell apoptosis via the intrinsic pathway and this may be one mechanism by which EtOH-induced stress responses lead to immunosuppression.