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.