肿瘤坏死因子α、γ干扰素和红细胞生成素与类风湿性关节炎贫血相关性研究

The correlation of cytokines TNFα,IFN γ, Epo with anemia in rheumatoid arthritis

目的 探讨类风湿性关节炎 (RA)伴慢性病性贫血 (ACD)的特征 ,及肿瘤坏死因子α(TNFα)、γ干扰素 (IFN γ)和红细胞生成素 (Epo)在其发病中的作用。方法 采用ELISA法检测RA患者血清TNFα、IFN γ水平及RA伴ACD患者的血清Epo变化。测定RA患者的铁代谢指标。观察TNFα、IFN γ对钴盐 (CoCl2 )诱导人肝癌细胞株 (HepG2 )Epo产生的影响及TNFα、IFN γ和Epo对正常骨髓CFU E和BFU E的影响 ;以及RA自身血清、Epo对RA骨髓CFU E的影响。结果 与正常对照组比较 ,RA及伴ACD者血清中TNFα、IFN γ均显著增高。TNFα、IFN γ与血清铁、血红蛋白浓度呈负相关。RA伴ACD者的Epo水平高于正常对照组 ,但低于同等贫血程度的单纯缺铁性贫血组 ,提示RA伴ACD者体内Epo相对不足。TNFα、IFN γ均能抑制钴盐 (CoCl2 )诱导的HepG2 的Epo生成 ,且这种抑制作用是特异性的而非毒性所致。TNFα、IFN γ抑制正常骨髓CFU E和BFU E集落形成 ,并呈剂量依赖性。RA自身血清能抑制其CFU E形成 ,而在胎牛血清培养基中RA自身的CFU E集落数与正常对照组相似。rhEpo能纠正TNFα、IFN γ和RA自身血清对红系祖细胞的抑制。结论 RA患者血清中存在造血干细胞抑制物。TNFα、IFN γ可能介导RA的ACD发病。

Objective To elucidate the characteristics of anemia of chronic disease(ACD) in rheumatoid arthritis(RA), and the role of TNFα,IFN γ and Epo in the pathogenesis of ACD. Method Serum TNFα and IFN γ levels in RA patients and serum Epo levels in RA with ACD were measured by ELISA. Serum iron status profile in RA patients were also detected. The effects of TNFα and IFN γ on cobalt induced erythropoietin production in human hepatic cancer cells(HepG 2) were examined. The effect of TNFα and IFN γ erythroid colony formation (CFU E and BFU E) of normal bone marrow cells, and the effect of serum from RA patients and Epo on CFU E yields of RA bone marrow cells. Result Serum TNFα or IFN γ in RA and RA with ACD patients were higher than those in normal controls, and were inversely correlated with hemoglobin, and serum iron levels. Serum Epo levels in ACD patients were lower than those in iron deficiency anemia patients with comparable hemoglobin level. TNFα and IFN γ could specifically inhibit cobalt induced Epo production in HepG 2 cells, and suppressed normal bone marrow BFU E and CFU E growth in a dose dependent manner. Bone marrow CFU E yields of RA patients were also suppressed by their own serum. The inhibitory effects of TNFα, IFN γ or serum from RA patients on erythroid colony formation could be corrected by the addition of rhEpo. Conclusion It suggested that there were hematopoietic inhibiting factors in the serum of RA patients. TNFα or IFN γ was involved in the pathogenesis of anemia in RA patients. Administration of rhEpo might be beneficial for anemia of RA patients.