Sgadari C, Angiolillo A L, Tosato G
Division of Hematologic Products, Food and Drug Administration, Bethesda, MD 20892, USA.
Blood. 1996 May 1;87(9):3877-82.
Interleukin 12 (IL-12), a multifunctional cytokine produced by macrophages and B-cell lines, induces interferon-gamma (IFN-gamma) production, stimulates growth of both T and natural killer cells, promotes Th1-type helper T-cell responses, and inhibits neovascularization. Because the human interferon-inducible protein 10 (IP-10) can also inhibit neovascularization, we tested whether IP-10, induced by IL-12 through the intermediate IFN-gamma, might be a mediator of IL-12 angiogenesis inhibition. We report here that murine IL-12 profoundly inhibited basic fibroblast growth factor (bFGF)-induced Matrigel neovascularization in vivo, and that this effect of IL-12 was neutralized by systemic administration of antibodies to either murine IFN-gamma or IP-10. Murine IL-12 induced murine IP-10 expression in mouse splenocytes, and human IFN-gamma induced human IP-10 expression in purified human endothelial cells, suggesting that IL-12 can induce IP-10 expression in certain cells. These results document the important role of IP-10 as a mediator of angiogenesis inhibition by IL-12, and raise the possibility that IP-10 may also contribute to the antitumor effect of IL-12.
白细胞介素12（IL-12）是一种由巨噬细胞和B细胞系产生的多功能细胞因子，可诱导γ干扰素（IFN-γ）生成，刺激T细胞和自然杀伤细胞生长，促进Th1型辅助性T细胞反应，并抑制新血管形成。由于人类干扰素诱导蛋白10（IP-10）也能抑制新血管形成，我们测试了由IL-12通过中间产物IFN-γ诱导产生的IP-10是否可能是IL-12抑制血管生成的介质。我们在此报告，小鼠IL-12在体内可显著抑制碱性成纤维细胞生长因子（bFGF）诱导的基质胶血管生成，并且通过全身给予抗小鼠IFN-γ或IP-10的抗体可中和IL-12的这一作用。小鼠IL-12可诱导小鼠脾细胞中IP-10表达，而人IFN-γ可诱导纯化的人内皮细胞中IP-10表达，这表明IL-12可在某些细胞中诱导IP-10表达。这些结果证明了IP-10作为IL-12抑制血管生成介质的重要作用，并提出了IP-10也可能有助于IL-12抗肿瘤作用的可能性。
