Elevated levels of inflammatory cytokines in bone marrow of patients with rheumatoid arthritis and anemia of chronic disease

Objective. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) play an important role in decreased erythropoiesis in patients with anemia of chronic disease (ACD) and rheumatoid arthritis (RA). Modulation of quantities of bone marrow erythroid progenitors during chronic inflammation may be one of the pathogenetic mechanisms leading to ACD. We studied bone marrow from patients with ACD with RA by investigating, first, local production of inflammatory cytokines in the bone marrow, and second, the relative fraction of late erythroid progenitors (erythropoietin and transferrin receptor positive cells; EpoR+ TrfR+) in bone marrow. In addition, the effects of TNF-α on EpoR+ TrfR+ cells were studied in vitro. Methods. Levels of IL-6 and TNF-α were measured by ELISA in supernatant of bone marrow and peripheral blood cultures from 14 patients with RA and ACD and 14 patients with RA without anemia. The numbers of EpoR+ TrfR+ cells in the bone marrow samples of both groups were assessed by 2 color fluorescence flow cytometry. Results. Levels of IL-6 and TNF-α were significantly higher in the supernatant of bone marrow cultures of patients with ACD compared to controls. No significant differences in the fraction of EpoR+ TrfR+ cells in samples was observed between the 2 groups of patients. Incubation of the samples with TNF-α did not result in modulation of the number of EpoR+ TrfR+ cells. Conclusion. Local production of proinflammatory cytokines in the bone marrow may be associated with the development of ACD in RA.