Possible role of tumor necrosis factor-alpha in erythropoietic suppression by endotoxin and granulocyte/macrophage colony-stimulating factor.
Injection of bacterial endotoxin or granulocyte/macrophage colony-stimulating factor (GM-CSF) into exhypoxic polycythemic mice simultaneously with erythropoietin (EPO) suppressed erythroid cell formation, as monitored by 59Fe incorporation into circulating red blood cells. This effect was dose-dependent and time-dependent. GM-CSF did not inhibit erythroid cell formation directly, as the antibody to the GM-CSF did not neutralize the effect of endotoxin, the inducer of GM-CSF. The suppression of both agents could be partially corrected by prior injection of a monoclonal antibody to tumor necrosis factor alpha (anti-TNF alpha). These results indicate that the suppression of EPO-induced erythroid cell formation by endotoxin and GM-CSF was due in part to the production of TNF alpha.
Udupa
K B
KB
Education and Clinical Center, V.A. Medical Center, Little Rock, AR 72205, USA.
Sharma
B G
BG
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007275:Injections, Intravenous; D007501:Iron / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004731:Endotoxins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007501:Iron