rh-erythropoietin stimulates immature reticulocyte release in man

The pharmacodynamics of single intravenous dosing with recombinant human erthropoietin (rhEPO) was investigated in eight healthy volunteers (150 U/kg, n = 2; 300 U/kg, n = 6) with respect to reticulocyte subdivisions (by fluorescence flow cytometry) and serum ferritin over 6.5 d. The present study shows that bolus rhEPO injection produces an immediate release of high and middle fluorescence (immature) reticulocytes with a high RNA content from the marrow into the circulation, whereas the low fluorescence (more mature) reticulocytes were at first not affected. Serum ferritin decreased markedly within 24 h, reaching a nadir 50% of baseline after 120 h (5 d), with no increase in haemoglobin. Our data suggests that rhEPO triggers premature expulsion of immature reticulocytes from the bone marrow into the circulation independent of its effect in stimulating erythropoiesis and that rhEPO has an effect on serum ferritin concentration which in this dynamic situation is dependent not only on the iron stores.