Ethanol activation of human natural cytotoxicity

Human lymphocytes cultured with ethanol and subsequently assayed for natural killer (NK) activity to K562 cells have enhanced NK activity compared to lymphocytes cultured without exposure to ethanol. Optimal enhancement occurred at 0.64% (v/v) ethanol, and required several hours of culture. Lymphocytes retained their enhanced cytolytic ability for several hours after removal from the ethanol-containing medium. The enhancement correlated with a faster rate of cytolysis by ethanol-treated lymphocytes, rather than recruitment of an increased number of killer cells, as measured with single cell assays. Inclusion of ethanol directly in the NK assays was inhibitory. Cells that had been cultured with ethanol were less sensitive to inhibition of NK activity by the proteinase substrate acetyl tyrosine ethyl ester than were control cells cultured without ethanol. Although this observation and the increased rate of cytolysis in the single cell assays are consistent with increased production of a chymotrypsin-like proteinase involved in cell-mediated cytotoxicity, no alteration in protein synthesis was detected concomitant with ethanol treatment. This report demonstrates that even without hepatic metabolism, ethanol can produce effects on lymphocyte function which remain after exposure to the reagent is discontinued.