MECHANISM OF ETHANOL-MEDIATED IMMUNOSUPPRESSION IN MICE - ETHANOL SUPPRESSES T-CELL PROLIFERATION WITHOUT AFFECTING IL2-PRODUCTION AND IL2-RECEPTOR EXPRESSION

The effect of extended ethanol consumption in young C57BL/6 mice on T-cell proliferation was studied. Splenic cells of young mice (3 - 4 months old), fed with one of three different liquid diets (5% ethanol, maltose-substitute, or standard liquid diet) for 28 - 38 days were cultured with plant lectins to assess T-cell proliferation and IL2 production, Expression of T-cell subset markers (CD4+/CD8+) was also determined. Then, Con A-activated T blast cells were assessed for their ability to express IL2 receptor (IL2R) and to respond to IL2. Finally, the proliferative response of splenic cells to PMA/ionomycin was assessed. The results showed that both lectin- and PMA/ionomycin-induced mitogenesis and IL2-dependent proliferation of T-cells from ethanol diet-fed mice were diminished as compared with that of maltose-substitute diet or standard liquid diet. However, the ability of T-cells from ethanol diet-fed mice to produce IL2 and to express IL2 R or CD4+/CD8+ subset markers was not affected. Furthermore, the magnitude of ethanol-mediated suppression of T-cell proliferation induced by PMA/ionomycin was comparable with that induced by Con A. These results taken together indicate that ethanol suppresses T-cell proliferation by interfering with events following the IL2 - IL2R interaction. Therefore, it is likely that ethanol inhibits murine T-cell proliferation by selectively affecting the progression (IL2R-mediated events) rather than the initiation (mitogenic receptor-mediated events) of the cell cycle.