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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。rhEpo能有效治疗RA贫血
Objective To investigate the characteristics of rheumatoid arthritis (RA) with chronic cerebral anemia (ACD) and the role of tumor necrosis factor α (TNFα), interferon γ (IFNγ) and erythropoietin (Epo) in the pathogenesis of rheumatoid arthritis (RA). Methods Serum levels of TNFα and IFN γ in patients with RA and serum Epo in RA patients with ACD were measured by ELISA. Determination of RA patients with iron metabolism indicators. To investigate the effects of TNFα and IFNγ on Epo production in HepG2 cells induced by cobalt chloride (CoCl2) and the effects of TNFα, IFNγ and Epo on CFU E and BFU E in normal bone marrow. Impact of CFU E Results Compared with the normal control group, the levels of TNFα and IFN γ in serum of RA and ACD patients were significantly increased. TNFα, IFN γ and serum iron, hemoglobin concentration was negatively correlated. The Epo level of RA with ACD was higher than that of normal control group, but the level of Epo was lower than that of pure iron deficiency anemia group, suggesting that Epo in RA with ACD was relatively insufficient. Both TNFα and IFNγ inhibited the HepG2-induced Epo production induced by cobalt chloride (CoCl2), and the inhibitory effect was specific rather than toxic. TNFα and IFNγ inhibited the formation of CFU E and BFU E colonies in normal bone marrow in a dose-dependent manner. RA autologous serum inhibited its CFU E formation, whereas RA itself had similar numbers of CFU E colonies in the fetal bovine serum medium as a normal control. rhEpo corrects the inhibition of erythroid progenitor cells by TNF [alpha], IFN [gamma] and RA autologous sera. Conclusions Hematopoietic stem cell inhibitors exist in the serum of RA patients. TNFα, IFNγ may mediate the onset of ACD in RA. rhEpo can effectively treat RA anemia