Antioxidants attenuate nuclear factor-kappa B activation and tumor necrosis factor-alpha production in alcoholic hepatitis patient monocytes and rat Kupffer cells, in vitro

There is increased tumor necrosis factor-α (TNF) activity in alcoholic hepatitis (AH). Objectives: To examine the effects of antioxidants and glutathione enhancing agents on NF-κB activation and TNF production in Kupffer cells and monocytes. Design and Methods: Isolated rat Kupffer cells and peripheral blood monocytes from AH patients were treated in vitro. NF-κB activation was assessed by electrophoretic mobility shift assay and TNF was measured in cell culture supernatants. Results: Monocytes from AH patients had greater TNF production compared to normal volunteers. Pretreatment with antioxidants or gluathione enhancing agents inhibited TNF production and NF-κB activation in both monocytes from normal and AH patients as well as in rat Kupffer cells. Conclusions: There may be a therapeutic role for antioxidants or glutathione enhancing agents in disease states with increased TNF activity such as AH.