Although alcohol itself has direct effects on cell function and signaling molecules, products of its metabolism have also been implicated in immunomodulatory effects (29, 50). In our experiments, CYP2E1, a major metabolizing enzyme of alcohol in macrophages was slightly up-regulated by chronic and not by acute alcohol treatment. Interestingly, alterations in NFκB binding activity and TNF-α production were independent of CYP2E1 activation, suggesting that the modulatory effects of alcohol on LPS signaling were direct and not due to its metabolites.
