Koren S, Klimpel G R, Fleischmann W R
J Biol Response Mod. 1986 Dec;5(6):571-80.
Colony stimulating factors have been shown to antagonize the bone marrow suppressive effects of interferons in vitro. The effect of partially purified murine macrophage colony stimulating factor (CSF-1) was evaluated for its ability to antagonize interferon's bone marrow suppressive effect and was measured for its effect against two other interferon activities. The effect of CSF-1 against interferon's bone marrow suppressive effect was measured in a bone marrow colony growth assay. The effect of CSF-1 against interferon's antiviral activity was measured in single-cycle vesicular stomatitis virus growth experiments. The effect of CSF-1 against interferon's antiproliferative activity was measured in 3-day cell growth kinetics assays using B-16 melanoma cells and J-774 reticulum sarcoma cells of macrophage origin. Each of the three types of interferon (MuIFN-alpha, MuIFN-beta, and MuIFN-gamma) were employed and had common effects, though they differed in the levels of their effective concentrations. Concomitant treatment with CSF-1 and interferon blocked the interferon mediated bone marrow suppression in a dose dependent manner but had no effect on the antiviral or antiproliferative activities of the interferons. Importantly, CSF-1 did not affect interferon's antiproliferative activity against the growth of J-774 reticulum sarcoma cells, even though CSF-1 is a macrophage colony stimulating factor and J-774 cells are of macrophage origin. The results suggest that colony stimulating factors might be employed to specifically protect bone marrow function during interferon therapy while not interfering with interferon's antiviral and antitumor activities.
集落刺激因子已被证明在体外可拮抗干扰素对骨髓的抑制作用。对部分纯化的小鼠巨噬细胞集落刺激因子(CSF-1)拮抗干扰素骨髓抑制作用的能力进行了评估,并测定了其对干扰素其他两种活性的影响。在骨髓集落生长试验中测定了CSF-1对干扰素骨髓抑制作用的影响。在单周期水泡性口炎病毒生长实验中测定了CSF-1对干扰素抗病毒活性的影响。在使用巨噬细胞来源的B-16黑色素瘤细胞和J-774网状细胞肉瘤细胞的3天细胞生长动力学试验中测定了CSF-1对干扰素抗增殖活性的影响。使用了三种类型的干扰素(MuIFN-α、MuIFN-β和MuIFN-γ),它们具有共同的作用,尽管其有效浓度水平有所不同。CSF-1与干扰素联合治疗以剂量依赖方式阻断了干扰素介导的骨髓抑制,但对干扰素的抗病毒或抗增殖活性没有影响。重要的是,CSF-1并不影响干扰素对J-774网状细胞肉瘤细胞生长的抗增殖活性,尽管CSF-1是一种巨噬细胞集落刺激因子,而J-774细胞是巨噬细胞来源。结果表明,集落刺激因子可用于在干扰素治疗期间特异性保护骨髓功能,同时不干扰干扰素的抗病毒和抗肿瘤活性。