EFFECTS OF RECOMBINANT-HUMAN-ERYTHROPOIETIN ON ANEMIC W/WV AND SL/SLD MICE

Summary. The effects of recombinant human erythropoietin (rHuEPO) on anaemic W/Wv and SI/SId mice were investigated. rHuEPO was injected every day for a week in doses up to 86000 iu/kg. Wv/+ and SId+ mice, which have genetically a weak anaemia, received 17 or 86 iu/kg of rHuEPO and showed dose‐dependent increases in haemoglobin, PCV, RBC and reticulocytes to the same extent as that in normal mice. W/Wv mice also showed increases in the haematological parameters in response to 8600 iu/kg of rHuEPO but the dose was much higher than that for normal mice. A reticulocyte increase in W/Wv mice appeared later than in normal mice and was not sustained for 2 weeks even though the rHuEPO treatment was continued. SI/SId mice, however, did not show any significant haematological effect from doses up to 86 000 iu/kg. In both W/Wv and SI/SId mice receiving 8600 and 86000 iu/kg of rHuEPO, respectively, an increase in splenic or bone marrow CFU‐E was observed regardless of the defect in their haemopoietic systems. The plasma erythropoietin (EPO) level in W/Wv and SI/SId mice was inversely correlated with the haemoglobin, indicating that EPO production was not influenced by the haemopoietic defect and was regulated by the hypoxic properties of the anaemia. These results indicate that a large dose of exogenous rHuEPO is effective for the anaemia in W/Wv mice caused by a stem cell defect but not for the anaemia in SI/SId mice caused by a defective microenvironment. Copyright © 1990, Wiley Blackwell. All rights reserved