Mulé J J, McIntosh J K, Jablons D M, Rosenberg S A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1990 Mar 1;171(3):629-36. doi: 10.1084/jem.171.3.629.
IL-6 possesses multiple biologic activities that affect a broad range of cells including those directly involved in immune responses as well as cells important in the systemic response to infection or trauma. We now show that purified human rIL-6, when administered alone at relatively high doses that are comparable to therapeutic levels of IL-2, mediated substantial reductions in the number of pulmonary and hepatic micrometastases from four distinct syngeneic tumors. Unlike IL-2, IL-6 injections resulted in neither observable toxicity nor death of the treated mice at the dose regimens used. Host immunosuppression by sublethal total-body irradiation before the initiation of therapy prevented the IL-6 antitumor effect, thus suggesting that IL-6 acted through a radiosensitive host component rather than directly on the tumor itself. Moreover, the systemic administration of relatively low doses of IL-6 in combination with subtherapeutic doses of TNF to mice bearing an established weakly immunogenic, syngeneic tumor at a subcutaneous site resulted in marked tumor regression and cure rates. These studies represent the first demonstration of tumor regression mediated by recombinant IL-6 in vivo.
白细胞介素-6具有多种生物学活性，可影响广泛的细胞，包括那些直接参与免疫反应的细胞以及在对感染或创伤的全身反应中起重要作用的细胞。我们现在表明，纯化的人重组白细胞介素-6在以与白细胞介素-2治疗水平相当的相对高剂量单独给药时，可介导来自四种不同同基因肿瘤的肺和肝微转移灶数量大幅减少。与白细胞介素-2不同，在所用剂量方案下，注射白细胞介素-6既未导致可观察到的毒性，也未导致受试小鼠死亡。在治疗开始前通过亚致死性全身照射进行宿主免疫抑制可阻止白细胞介素-6的抗肿瘤作用，因此表明白细胞介素-6是通过放射敏感的宿主成分起作用，而不是直接作用于肿瘤本身。此外，将相对低剂量的白细胞介素-6与亚治疗剂量的肿瘤坏死因子联合全身给药给皮下接种已建立的弱免疫原性同基因肿瘤的小鼠，可导致明显的肿瘤消退和治愈率。这些研究首次证明了重组白细胞介素-6在体内介导的肿瘤消退。
