EFFECT OF SUCCINIC ACID MONOMETHYL ESTER ON INTERLEUKIN-1-BETA CYTOTOXICITY IN TUMORAL PANCREATIC-ISLET CELLS

Interleukin-1 beta (IL-1 beta), tested at a concentration of 1.25 ng m L(-1), stimulated NO production, exerted a cytotoxic action, inhibited [H-3] incorporation, augmented D-[5-H-3]glucose utilisation and impai red D-[6-C-14]glucose oxidation in tumoural pancreatic islet cells of the RINm5F line. These effects of the cytokine were suppressed by N-mo nomethyl-L-arginine (1.0 mM). The monoethyl eater of succinic acid (10 .0 mM) failed, however, to protect the RINm5F cells against the cytoto xic and metabolic effects of IL-1 beta, at variance with the situation previously documented in normal islet cells. It is proposed that such a discrepancy is attributable, in part at least, to the vastly differ ent contribution of mitochondrial oxidative events to overall ATP gene ration in tumoural, as distinct from normal, islet cells.