Interaction of interleukin-1 and interferon-gamma on fibroblast growth factor-induced angiogenesis.

The interaction of interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) actions on several aspects of angiogenesis in vitro and in vivo was studied. The proliferation and migration of human umbilical vein endothelial cells cultured with basic fibroblast growth factor (bFGF) were synergistically inhibited by cotreatment with IL-1 and IFN-gamma. Endothelial cell adhesion to collagen was suppressed by IL-1 and the effect was slightly enhanced by the combination of IL-1 and IFN-gamma. Local administration of IL-1 (10,000 U) and IFN-gamma (1,000 U) inhibited bFGF-induced angiogenesis in the skin of mice, and synergistic inhibitory activity of the combination was demonstrated. Expression of FGF receptors was strongly downregulated by the combination, whereas expressions of epidermal growth factor (EGF) receptors, integrin beta 1 and integrin beta 3 were not. EGF partially abrogated the growth-inhibitory effects of IL-1 and IFN-gamma. These findings indicate that IL-1 and IFN-gamma are each able to act an angiogenesis inhibitor in a situation where FGF plays a major role in angiogenesis, and the activity is synergistically enhanced when they are used in combination.