Defibrotide protects endothelial cells, but not L929 tumour cells, from tumour necrosis factor-alpha-mediated cytotoxicity.

The effect of defibrotide on the cytotoxicity of tumour necrosis factor-alpha was investigated in cultured bovine pulmonary artery endothelial cells and L929 mouse tumour cells. In endothelial cells, a 72-h incubation with tumour necrosis factor-alpha (1 and 10 ng mL-1) reduced the number of viable cells to 63 and 51% of control, respectively. Simultaneous incubation with defibrotide (0.03-0.3 mg mL-1) protected endothelial cells from tumour necrosis factor-alpha-mediated cytotoxicity, and increased viability in a concentration-dependent fashion to 98% of control at 1 ng mL-1 tumour necrosis factor-alpha and to 80% of control at 10 ng mL-1 tumour necrosis factor-alpha. However, under the same conditions a similar cytotoxic response to tumour necrosis factor-alpha in L929 tumour cells remained unaltered in the presence of defibrotide. These findings demonstrate protection from tumour necrosis factor-alpha-mediated toxicity by defibrotide in endothelial cells but not in a tumour cell line. It is concluded that defibrotide might serve as a therapeutic agent to limit the vascular toxicity of tumour necrosis factor-alpha without affecting its antineoplastic activity.