Mumps virus infection increases sensitivity to tumour necrosis factor-alpha and gamma-interferon induced cytotoxicity in a human insulinoma cell line

Gamma-interferon (gamma-IFN) and tumour necrosis factor-alpha (TNF-alpha) have been suggested as possible effector molecules of the cytotoxic beta-cell injury leading to Type I (insulin-dependent) diabetes mellitus. In this study we evaluated the cytotoxicity induced by gamma-IFN and TNF-alpha on a human insulinoma cell line infected with mumps virus and compared this with non-infected cells, A reduction of 50% in the viability of non-infected cells was observed with 100 IU/ml of gamma-IFN or with 25 IU/ml gamma-IFN + 25 IU/ml TNF-alpha in combination, Cells infected with mumps virus showed a 50% reduction of viability with 25 IU/ml of gamma-IFN, and with 12 IU/ml gamma-IFN + 12 IU/ml TNF-alpha in combination, Up to 1000 IU/ml of TNF-alpha alone was not cytotoxic to beta-cells in vitro, but TNF-alpha at a concentration of 100 IU/ml reduced viral infected cell viability by 50%, The reduction in cell viability due to the infection alone was < 5%, These data demonstrate that mumps virus infected beta-cells are more susceptible to the cytotoxic damage caused by cytokines, The high susceptibility of infected beta-cells to cytokine-mediated injury following viral infection may contribute to beta-cell damage occurring in vivo in Type I diabetes.