Antitumor activity of recombinant interleukin 6 in mice.
Antitumor activity of recombinant interleukin 6 in mice.
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DOI：
10.1084/jem.171.3.629
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发表时间：
1990-03-01
期刊：
影响因子：
--
通讯作者：
Rosenberg SA
中科院分区：
文献类型：
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作者：
Mulé JJ;McIntosh JK;Jablons DM;Rosenberg SA
IL-6具有多种生物学活性，影响广泛的细胞，包括那些直接参与免疫反应的细胞，以及在全身对感染或创伤的反应中至关重要的细胞。我们现在发现，当单独给予相当于治疗水平的IL-2的相对高剂量的纯化的人rIL-6时，可以显著减少四种不同的同基因肿瘤的肺和肝脏微转移的数量。与IL-2不同的是，在所使用的剂量方案下，IL-6注射既不会导致可见的毒性，也不会导致治疗小鼠的死亡。在治疗开始前，通过亚致死性全身照射的宿主免疫抑制阻止了IL-6的抗肿瘤作用，因此提示IL-6通过辐射敏感的宿主成分而不是直接作用于肿瘤本身。此外，对皮下已有弱免疫原性同基因肿瘤的小鼠，全身给予相对较低剂量的IL-6和亚治疗剂量的肿瘤坏死因子，可导致显著的肿瘤消退和治愈率。这些研究首次证实了重组IL-6在体内介导的肿瘤消退。
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.