Effect of Erythropoietin on Granulocytopoiesis: In Vitro and in Vivo Studies in Weanling Rats

Abstract

ABSTRACT: In clonogenic assays, high concentrations of erythropoietin (epo) result in reduced generation of neutrophils from progenitors. Fetal progenitors appear to be more sensitive to this effect than are those of adults. Neutropenia has not been observed, however, as a complication of epo administration to anemic adults. Nevertheless, we remained concerned that diminutions in the neutrophil proliferative or storage pools might occur in epo-treated neonates. Therefore, after establishing that epo induces down-modulation of neutrophil generation in vitro from progenitors of weanling rats, we administered high doses of epo and subsequently performed neutrophil kinetic studies. Six pairs of 8-9-d-old rats were given three daily injections of 2000 IU/kg of either epo or a control. Fortyeight h later, the epo recipients had elevations in reticulocytes, circulating normoblasts, and hematocrits, as well as in splenic and femoral normoblasts and mature erythroid progenitors. However, no changes were observed in concentrations of circulating neutrophils, monocytes, or lymphocytes. In addition, no changes were observed in the splenic or marrow neutrophil storage or proliferative pools, or the pools of granulocyte-macrophage progenitors or multipotent progenitors. Thus, although in vitro high concentrations of epo resulted in diminished generation of neutrophils from progenitors, no reductions were observed in vivo using epo doses 4- to 40-fold higher than those generally administered to humans.

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