To elucidate the characteristics of anemia of chronic disease(ACD) in rheumatoid arthritis(RA), and the role of TNF alpha, IFN-gamma and Epo in the pathogenesis of ACD.
Serum TNF alpha and IFN-gamma 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 TNF alpha and IFN-gamma on cobalt-induced erythropoietin production in human hepatic cancer cells(HepG2) were examined. The effect of TNF alpha and IFN-gamma 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.
Serum TNF alpha or IFN-gamma 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. TNF alpha and IFN-gamma could specifically inhibit cobalt-induced Epo production in HepG2 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 TNF alpha, IFN-gamma or serum from RA patients on erythroid colony formation could be corrected by the addition of rhEpo.
It suggested that there were hematopoietic inhibiting factors in the serum of RA patients. TNF alpha or IFN-gamma was involved in the pathogenesis of anemia in RA patients. Administration of rhEpo might be beneficial for anemia of RA patients.