Role of Kupffer cells in alcoholic hepatitis

Kupffer cells play a major role in alcoholic liver disease. Oxidative stress and endotoxin are major mediators of the inflammatory process in alcoholic hepatitis. Recent evidence supports the suggestion that endotoxin-induced signal transduction begins with CD14-mediated activation of Toll-receptor 4 and subsequent activation of nuclear factor-kappa B (NF-kappaB) binding activity. Free radicals from reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in Kupffer cells also activate NF-kappaB binding activity. Inflammatory cytokines and cyclooxygenase-2 are up-regulated in response to binding of NF-kappaB. A combined role for tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-22 is important in the pathogenesis of alcoholic hepatitis. (C) 2002 Elsevier Science Inc. All rights reserved.