Schwarz M A, Hamilton L D, Tardelli L, Narula S K, Sullivan L M
Immunology Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
J Immunother Emphasis Tumor Immunol. 1994 Aug;16(2):95-104. doi: 10.1097/00002371-199408000-00003.
Interleukin-10 (IL-10), originally identified as an inhibitor of cytokine and monokine synthesis [e.g., IL-2, interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF-alpha)], modulates a wide range of immunologic activities. In the present study we have examined the induction of non-major histocompatibility complex-restricted cytolytic activity in human peripheral blood mononuclear cells (PBMCs). PBMCs incubated with human IL-10 for 3 days were used as effector cells in cytotoxicity (i.e., 51Cr release) assays against a panel of human tumor cells. In a concentration-dependent manner. IL-10 stimulated or potentiated lytic activity against several human tumor cell lines. Induction of cytolytic activities by IL-10 was neutralized by anti-IL-10 monoclonal antibodies but not by antibodies against IFN-gamma or TNF-alpha. Co-incubation of PB-MCs with IL-10 and IL-2 or IL-10 and IFN-alpha augmented cytolytic activity, in particular at lower effector-to-target ratios. IL-2-induced release of TNF-alpha was dramatically reduced by IL-10; however, the expression of lymphokine-activated killer (LAK) activity was not affected. PBMCs preactivated with IL-10 before addition of IL-2 displayed higher levels of LAK activity. Inhibition of IL-2-driven LAK activity by IL-4 is alleviated by IL-10. Finally, IL-10 is not affected by inhibitors of IL-2, such as IL-4 and transforming growth factor-beta. Potential application of IL-10 to anti-tumor therapies is discussed.
白细胞介素-10（IL-10）最初被鉴定为细胞因子和单核因子合成的抑制剂[如白细胞介素-2、干扰素-γ（IFN-γ）和肿瘤坏死因子（TNF-α）]，可调节广泛的免疫活性。在本研究中，我们检测了人外周血单个核细胞（PBMC）中非主要组织相容性复合体限制的细胞溶解活性的诱导情况。将与人IL-10孵育3天的PBMC用作效应细胞，针对一组人肿瘤细胞进行细胞毒性（即51Cr释放）测定。IL-10以浓度依赖的方式刺激或增强了对几种人肿瘤细胞系的溶解活性。IL-10诱导的细胞溶解活性被抗IL-10单克隆抗体中和，但未被抗IFN-γ或TNF-α抗体中和。PBMC与IL-10和IL-2或IL-10和IFN-α共同孵育可增强细胞溶解活性，尤其是在较低的效应细胞与靶细胞比例下。IL-10显著降低了IL-2诱导的TNF-α释放；然而，淋巴因子激活的杀伤细胞（LAK）活性的表达未受影响。在添加IL-2之前用IL-10预激活的PBMC表现出更高水平的LAK活性。IL-10可减轻IL-4对IL-2驱动的LAK活性的抑制作用。最后，IL-10不受IL-2抑制剂如IL-4和转化生长因子-β的影响。本文讨论了IL-10在抗肿瘤治疗中的潜在应用。
