Defibrotide Protects Endothelial Cells, but not L929 Tumour Cells, from Tumour Necrosis Factor‐α‐mediated Cytotoxicity

The effect of defibrotide on the cytotoxicity of tumour necrosis factor‐α 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‐α (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‐α‐mediated cytotoxicity, and increased viability in a concentration‐dependent fashion to 98% of control at 1 ng mL⁻¹ tumour necrosis factor‐α and to 80% of control at 10 ng mL⁻¹ tumour necrosis factor‐α. However, under the same conditions a similar cytotoxic response to tumour necrosis factor‐α in L929 tumour cells remained unaltered in the presence of defibrotide. These findings demonstrate protection from tumour necrosis factor‐α‐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‐α without affecting its antineoplastic activity. 1995 Royal Pharmaceutical Society of Great Britain