Cytotoxic effects of cytokines on rat islets: evidence for involvement of free radicals and lipid peroxidation.

We have previously reported that oxygen free radical scavengers protect rat islet cells from damage by cytokines and we interpreted these findings as suggesting the involvement of oxygen free radicals but did not directly measure indices of free radical activity. In this study, we report on malondialdehyde, an end product of lipid peroxidation, in rat islets incubated with cytokines. The individual cytokines, interleukin 1 (1 U/ml), tumour necrosis factor (10(2) U/ml), and interferon gamma (10(2) U/ml) inhibited insulin release but did not increase islet malondialdehyde levels. Combination of these cytokines however, produced significant increases in islet malondialdehyde and this was accompanied by islet necrosis. Furthermore, an inhibitor of lipid peroxidation, U78518E, significantly decreased the cytokine-induced increase in islet malondialdehyde and protected islet Beta cells from destruction by the cytokine combination of interleukin 1, tumour necrosis factor and interferon gamma. These findings suggest that the cytotoxic action of cytokines on islet Beta cells may result from free radical production and lipid peroxidation in the islet cells.