RH-ERYTHROPOIETIN STIMULATES IMMATURE RETICULOCYTE RELEASE IN MAN

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