NITRIC-OXIDE MEDIATES TUMOR-NECROSIS-FACTOR-ALPHA CYTOTOXICITY IN ENDOTHELIAL-CELLS

Tumor necrosis factor alpha (TNF-α) exerts multiple actions on endothelial cells including among others the expression of pro-coagulant activity and adhesion molecules, and secretion of cytokines. We now show that TNF-α induces a time- and dose-dependent cytotoxic effect on cultured bovine aortic endothelial cells. This TNF-induced cytotoxicity, which is preceded by increased production of nitric oxide (NO), is significantly decreased by the NO synthase inhibitor N-iminoethyl-Lornithine (L-NIO). Dexamethasone, which prevents the expression of cytokine-induced NO synthase in endothelial cells, also inhibits TNF-α-dependent cytotoxicity. The results indicate that NO is involved in the cytotoxic effect of TNF-α on endothelial cells. © 1992 Academic Press, Inc.