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- _2 value "The establishment of the role of IL-18 in inflammation and RA led to the question of its angiogenic potential. In this study, we examined the capacity of IL-18 to mediate angiogenesis in in vitro and in vivo models. We further compared the angiogenic activity of IL-18 with that of known mediators, such as bFGF. One potential mechanism of the angiogenic activity of IL-18 that we examined is through the involvement of avb3 integrin (34). This role of avb3 was examined in the IL-18-induced migration of endothelial cells. IL-18 induced tube formation in Matrigel matrix in vitro. To examine the role of IL-18 in angiogenesis in vivo, we also implanted IL-18 in Matrigel plugs in mice, and found a significant increase in blood vessel formation over control, as measured by hemoglobin concentration. This effect was not decreased by implanting neutralizing anti-TNF-a Ab in the Matrigel plug. Finally, in an alternative model of angiogenesis, a wound granuloma model, we implanted sponge discs embedded with IL-18 into mice and showed a 4-fold increase in angiogenesis compared with controls. These findings support a novel role for IL-18 as an angiogenic mediator in RA and may elucidate a potential therapeutic target for angiogenesis-directed disease." provenance.