γ-干扰素对骨吸收及实体瘤骨转移的体外抑制作用

INHIBITORY EFFECT OF INF-γ ON BONE RESORPTION AND BONE METASTASIS OF SOLID TUMOR IN VITRO

目的探讨体外实验中γ-干扰素(IFN-γ)对其他细胞因子引起的骨吸收及实体瘤骨转移病人外周血单个核细胞培养上清(PBMCs)促进的骨吸收的抑制作用。方法利用新生鼠头顶骨进行体外骨吸收实验,分别验证细胞因子白细胞介素1(IL-1)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、IFN-γ、粒-巨噬细胞生长因子(GM-CSF)在体外对骨吸收的影响。检测8例实体瘤骨转移阴性及11例骨转移阳性病人PBMCs的骨吸收活性(BRA)。结果IL-1I、L-6、TNF、GM-CSF均可促进体外骨吸收,以IL-1作用最强。而上述因子联合培养,BRA明显增强。IFN-γ本身对骨吸收作用不明显,但能使IL-1及细胞因子联合培养引起的骨吸收减弱。IFN-γ可使实体瘤骨转移阳性病人PBMCs诱发的BRA增强明显降低(t=2.34,P<0.05)。结论IL-1I、L-6、TNF、GM-CSF在体外对骨吸收有促进作用;IFN-γ在体外可使部分细胞因子及实体瘤骨转移阳性病人PBMCs促进的骨吸收作用减弱,提示γ-干扰素可能存在抑制肿瘤转移作用。

Objective To explore the inhibitory effect of IFN-γ on bone resorption stimulated by cytokines and peripheral blood mononuclear cells cultural supernatant （PBMCs） of solid tumor patients with bone metastasis. Methods Bone resorption test was carried out using neonatal mouse calvaria to investigate the bone resorbing activity （BRA） of cytokines （IL-1, IL-6, TNF, GM-CSF, and IFN-γ）. The BRA of PBMCs of 19 cases of solid tumor patients with or without bone metastasis and its interaction with IFN-γ were tested. Results IL-1,IL-6,TNF, and GM-GSF could stimulate bone resorption, and IL-1 was the most potent stimulator, but when these cytokines were co-cultured, the BRA was significantly strengthened. IFN-γ itself had no evident effect on bone resorption, but it could ameliorate bone resorption induced by other eytokines. IFN-γ could inhibit the BRA induced by PBMCs of solid tumor patients with multiple bone metastasis significantly, as compared with the control group without IFN-γ（t= 2.34,P〈0.05）. Conclusion IFN-γ could reduce the BRA strengthened by some cytokines and PBMCs of patients with bone metastasis of solid tumors, which suggests that IFN-γ may inhibit hone metastasis in solid tumors.