Naldini A, Fleischmann W R
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
J Biol Response Mod. 1987 Oct;6(5):546-55.
Interferon treatment has been shown to cause myelosuppression in man and in a mouse model. Combinations of interferon-gamma (IFN-gamma) with either interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta) cause the synergistic enhancement of interferons' antiviral, antiproliferative, antitumor, and immunoregulatory activities. Thus, combinations of MuIFN-beta and either natural or recombinant DNA-derived MuIFN-gamma were evaluated for their ability to cause the synergistic enhancement of interferon's myelosuppressive activity. The combinations of interferons were evaluated in vitro in bone-marrow colony-stimulating assays. They were seen to potentiate the in vitro myelosuppressive effect of the interferons. The combinations were evaluated for their in vivo myelosuppressive effect in mice. Treatment with the separate interferons caused a significant reduction in the number of circulating leukocytes, suggesting a potent myelosuppressive effect. However, treatment with the interferons in combination caused an antagonism and led to a myelosuppressive effect which was no greater than that of the interferons alone. The combinations of interferons were employed at concentrations which have been shown to provide substantial potentiation of the antitumor action of the interferons against B-16 melanoma. Thus, the data suggest that combination interferon therapy employing IFN-gamma together with either IFN-alpha or IFN-beta provide a potentiated antitumor activity without increasing the myelosuppressive side effect of the therapy.
干扰素治疗已被证明在人体和小鼠模型中会引起骨髓抑制。γ干扰素（IFN-γ）与α干扰素（IFN-α）或β干扰素（IFN-β）联合使用，可协同增强干扰素的抗病毒、抗增殖、抗肿瘤和免疫调节活性。因此，对鼠源IFN-β与天然或重组DNA来源的鼠源IFN-γ联合使用时增强干扰素骨髓抑制活性的能力进行了评估。在体外骨髓集落刺激试验中对干扰素组合进行了评估。结果发现它们可增强干扰素在体外的骨髓抑制作用。对这些组合在小鼠体内的骨髓抑制作用进行了评估。单独使用干扰素治疗导致循环白细胞数量显著减少，表明有强大的骨髓抑制作用。然而，联合使用干扰素治疗产生了拮抗作用，导致骨髓抑制作用并不比单独使用干扰素时更强。所使用的干扰素组合浓度已被证明能显著增强干扰素对B-16黑色素瘤的抗肿瘤作用。因此，数据表明，将IFN-γ与IFN-α或IFN-β联合进行干扰素联合治疗，可在不增加治疗骨髓抑制副作用的情况下增强抗肿瘤活性。
