Aderka D, Le J M, Vilcek J
Department of Microbiology, New York University Medical Center 10016.
J Immunol. 1989 Dec 1;143(11):3517-23.
Incubation of the human U937 histiocytic lymphoma cell line with granulocyte-macrophage colony stimulating factor (GM-CSF) rendered the cells responsive to induction of TNF by LPS. Treatment with IL-6 reduced TNF production in GM-CSF-primed U937 cells. The inhibitory effect was most pronounced (approximately equal to 80%) when IL-6 was added either along with GM-CSF or within the first 3 h of GM-CSF treatment. Both GM-CSF or IL-6 inhibited [3H]TdR uptake in U937 cells, and simultaneous treatment with GM-CSF and IL-6 resulted in an additive inhibitory effect on cell proliferation. However, the inhibition of TNF production could not be explained by the inhibitory effect of IL-6 on cell growth, nor was it due to a reduction in cell viability. An inhibition of TNF production by IL-6 was also demonstrated in cultured human peripheral blood monocytes. Treatment with IL-6 also resulted in a dose-dependent reduction of the 17-kDa TNF band revealed by SDS-PAGE after labeling monocytes with [35S]cysteine and immunoprecipitation with anti-TNF mAb. In addition, treatment with IL-6 resulted in a reduction of monocyte in vitro cytotoxicity for tumor target cells. Finally, in mice sensitized by the administration of Bacillus Calmette-Guérin, the injection of IL-6 significantly reduced the levels of TNF found in the serum upon challenge with LPS. Inasmuch as TNF is known to be an inducer of IL-6, the inhibitory action of IL-6 on TNF production may represent the negative arm of a regulatory circuit. The inhibitory action of IL-6 on TNF production is consistent with a predominantly antiinflammatory role of IL-6 in the intact organism.
用人粒细胞-巨噬细胞集落刺激因子（GM-CSF）培养人U937组织细胞淋巴瘤细胞系，可使细胞对脂多糖（LPS）诱导肿瘤坏死因子（TNF）产生反应。用白细胞介素-6（IL-6）处理可降低GM-CSF预处理的U937细胞中TNF的产生。当IL-6与GM-CSF同时添加或在GM-CSF处理的前3小时内添加时，抑制作用最为明显（约80%）。GM-CSF或IL-6均可抑制U937细胞中[3H]胸腺嘧啶核苷（TdR）的摄取，GM-CSF和IL-6同时处理对细胞增殖产生累加抑制作用。然而，IL-6对TNF产生的抑制作用无法用其对细胞生长的抑制作用来解释，也不是由于细胞活力降低所致。在培养的人外周血单核细胞中也证实了IL-6对TNF产生的抑制作用。用IL-6处理还导致在用[35S]半胱氨酸标记单核细胞并用抗TNF单克隆抗体进行免疫沉淀后，十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）显示的17-kDa TNF条带呈剂量依赖性减少。此外，用IL-6处理导致单核细胞对肿瘤靶细胞的体外细胞毒性降低。最后，在用卡介苗致敏的小鼠中，注射IL-6可显著降低LPS攻击后血清中TNF的水平。鉴于已知TNF是IL-6的诱导剂，IL-6对TNF产生的抑制作用可能代表调节回路的负向调节臂。IL-6对TNF产生的抑制作用与IL-6在完整机体中主要的抗炎作用一致。
