Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade.
Davis D., Charles PJ., Potter A., Feldmann M., Maini RN., Elliott MJ.
Anaemia of chronic disease (ACD) is a common feature of active rheumatoid arthritis (RA). Inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), are thought to contribute to the pathogenesis of ACD, possibly by inhibiting erythropoietin (EPO) production. In this study, we examined the in vivo effects of TNF-alpha blockade with a chimeric monoclonal antibody, cA2, on erythropoiesis in RA patients with ACD. Administration of cA2 led to a dose-dependent increase in haemoglobin levels compared to placebo and these changes were accompanied by a reduction in both EPO and IL-6 levels. The data support the notion that TNF-alpha is important in the causation of ACD, but suggest a mechanism independent of EPO suppression. Instead, TNF-alpha may act directly on bone marrow red cell precursors.