Growth inhibition of human endothelial cells by human recombinant tumor necrosis factor alpha and interferon-gamma

We investigated the effect of recombinant tumor necrosis factor-alpha (rTNF-alpha) on the proliferative response of human umbilical vein endothelial cells (HUVEC) to normal human serum (NHS), in the absence or the presence of interferon (IFN)-gamma. rTNF-alpha significantly impaired NHS-stimulated HUVEC growth at a dose as low as 0.1 U/ml. The inhibitory effect of rTNF-alpha was dose-dependent up to 50-100 U/ml and was already evident after 2 h of incubation. Doses of rTNF-alpha in the range of 10 U/ml completely suppressed 3H-thymidine uptake stimulated by 7.5% NHS, and the effect was partially overcome by 10-20% NHS. rTNF-alpha was not cytotoxic at doses up to 1000 U/ml. rIFN-gamma was also effective in suppressing NHS-stimulated 3H-thymidine incorporation, and at low doses (0.1 U/ml) rIFN-gamma and rTFN-alpha showed an additive effect. The effect of TFN-alpha and IFN-gamma in antagonizing the proliferative response of vascular endothelium to the variety of growth factors contained in human serum could be relevant in a variety of pathologic conditions involving endothelium damage and proliferation.