Inhibition by interleukin‐1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias

Summary. Highly purified and cloned preparations of interleukin‐1 (IL‐1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL‐1 and purified and cloned human IL‐1α and IL‐1β were approximately equipotent in this assay. IL‐1 inhibited the proliferation response of EPC even when added as long as 17h after Epo, suggesting that IL‐1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL‐1 on Epo‐induced proliferation, and PGE2 had no demonstrable effect on the process. Tumornecrosis factor‐α and interferons β1, and γ did not affect Epoinduced proliferation. It is suggested that IL‐1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant‐cell arteritis, graft‐versus‐host disease and disorders associated with lymphocyte‐mediated suppression of erythropoiesis.