Ethanol-induced macrophage apoptosis: The role of TGF-beta

Both clinical and laboratory reports indicate that ethanol addicts are pron e to recurrent infections, We hypothesize that ethanol promotes macrophage apoptosis, thus compromising the efficiency of the mononuclear phagocyte sy stem in dealing with infection. We studied the effect of ethanol on macroph age apoptosis. Human monocytes isolated from healthy subjects after an alco hol drinking binge showed enhanced apoptosis (before, 1.2 +/- 0.3% vs after , 28.4 +/- 3.7% apoptotic cells/field). Peritoneal macrophages harvested fr om ethanol-treated rats also showed increased (p < 0.0001) apoptosis, DNA i solated from peritoneal macrophages of ethanol-treated rats displayed integ er multiples of 200 base pairs (ladder pattern). Furthermore, macrophages h arvested from ethanol-treated rats had an enhanced expression as well as ac cumulation of TGF-beta. In in vitro studies, ethanol promoted apoptosis of human monocytes as well as rat peritoneal macrophages. In addition, ethanol enhanced apoptosis of murine macrophages (J774) in a time-dependent manner . The ethanol-induced apoptosis was amplified by LPS and partly attenuated (p < 0.001) by anti-TGF-beta Ab, TGF-beta also promoted macrophage apoptosi s in a dose-dependent manner. Moreover, ethanol enhanced TGF-beta protein p roduction by macrophages. These results indicate that ethanol promotes macr ophage apoptosis, This effect of ethanol seems to be partly mediated throug h the generation of TGF-beta by macrophages.