Protective effect of nicotinamide and 3-aminobenzamide on islet cell damage induced by gamma-interferon and tumor necrosis factor.

Mouse islet cell monolayers were damaged when cultured for five days in a medium containing 200 U/ml of recombinant murine interferon-gamma (IFN-gamma) and 300 U/ml of recombinant tumor necrosis factor (TNF). The cells formed granular clusters and ultimately floated in the medium; the floating cells proved to be dead by the trypan-blue dye-exclusion method. When 20 mM of nicotinamide or 5 mM of 3-aminobenzamide was supplemented to the medium, islet cell monolayers remained in the presence of the cytokines. 51Cr release studies showed that specific 51Cr release during five-day incubation with 200 U/ml of IFN-gamma and 300 U/ml of TNF was 30 +/- 4% (mean +/- SE). In a medium containing 20 mM of nicotinamide, together with IFN-gamma and TNF, specific 51Cr release was significantly reduced (12 +/- 3%, p less than 0.01). 3-aminobenzamide was effective at the level of 5 mM; specific 51Cr release was 2 +/- 5% (p less than 0.01). These results suggest that the mechanism by which IFN-gamma and TNF damage islet cells may be similar to that of streptozotocin and/or alloxan.