Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias.
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-1 alpha and IL-1 beta were approximately equipotent in this assay. IL-1 inhibited the proliferation response of EPC even when added as long as 17 h 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. Tumor-necrosis factor-alpha and interferons beta 1, and gamma did not affect Epo-induced 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.
D000740:Anemia / Q000209:etiology; D000741:Anemia, Aplastic / Q000473:pathology*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004900:Erythroblasts / Q000187:drug effects; D004921:Erythropoietin / Q000037:antagonists & inhibitors*; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D013154:Spleen / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006131:Growth Inhibitors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin