Increased monocyte nuclear factor-kappa B activation and tumor necrosis factor production in alcoholic hepatitis

Increased tumor necrosis factor-a activity has been reported in patients wi th alcoholic hepatitis and is implicated in its pathogenesis. The aim of th is study was to investigate potential mechanisms of increased tumor necrosi s factor-a activity in alcoholic hepatitis. Monocyte nuclear factor-kb acti vity was assessed by electrophoretic mobility shift assay, monocyte tumor n ecrosis factor-a mRNA was semiquantitatively assessed by reverse transcript ase polymerase chain reaction, and tumor necrosis factor-a in monocyte cult ure supernatants was measured. There was significantly greater spontaneous nuclear factor-kB activity in the monocytes of 6 patients with alcoholic he patitis as compared with that in the monocytes of control subjects. There w as spontaneous tumor necrosis factor-a mRNA and tumor necrosis factor-a rel ease from the monocytes of patients with alcoholic hepatitis but not from t he monocytes of normal subjects. Endotoxin increased nuclear factor-kB acti vity and induced tumor necrosis factor-a mRNA and tumor necrosis factor-a r elease from normal subjects' monocytes, Endotoxin further increased nuclear factor-ks activity, tumor necrosis factor-a mRNA, and tumor necrosis facto r-a release from the monocytes of patients with alcoholic hepatitis. Supers hift assays indicate that the monocyte nuclear factor-kB activation involve s the p50 and p65 subunits, Dysregulated tumor necrosis factor-a metabolism in alcoholic hepatitis monocytes is associated with increased nuclear fact or-kB activity and tumor necrosis factor-a mRNA expression.