EFFECTS OF FREE-RADICAL SCAVENGERS ON CYTOKINE ACTIONS ON ISLET CELLS

We investigated the effect of free radical scavengers on the actions o f cytokines on islet cells. Interferon-gamma and tumor necrosis factor -alpha reduced the nicotinamide adenine dinucleotide content of mouse islet cells: the combination of interferon-gamma (4 x 10(5) U/1) and t umor necrosis factor-alpha (4 x 10(5) U/1) caused nicotinamide adenine dinucleotide reduction by approximately 40%. Dimethyl urea and dimeth yl sulfoxide prevented the decrease, whereas superoxide dismutase. cat alase, and mannitol were not effective. Dimethyl urea and dimethyl sul foxide protected islet cells from the synergistic cytotoxic action of interferon-gamma and tumor necrosis factor-alpha. Major histocompatibi lity complex class II antigen induction by interferon-gamma and tumor necrosis factor-alpha was also inhibited by dimethyl urea and dimethyl sulfoxide, but not by superoxide dismutase. catalase and mannitol. Si nce superoxide dismutase of a membrane-penetrable form attenuated the class II antigen induction, the inefficiency of superoxide dismutase, catalase and mannitol may be attributable to their inability to penetr ate islet cells. These results suggest that the intracellular generati on of free oxygen radicals is involved in islet cell cytotoxicity and class II molecule expression by interferon-gamma and tumor necrosis fa ctor-alpha, and that nicotinamide adenine dinucleotide reduction may b e associated with islet cell dysfunction caused by the cytokines.