EFFECTS OF RECOMBINANT-HUMAN-ERYTHROPOIETIN AND INTERLEUKIN-3 ON ERYTHROPOIETIC RECOVERY FROM ACUTE ANEMIA

The risks inherent in the use of homologous blood products have increa sed efforts toward identifying alternatives to transfusion. We have pr eviously shown that the administration of recombinant human erythropoi etin (rhEpo) enhances the erythropoietic response to acute blood loss. Recombinant human interleukin-3 (rh-IL3) is a hematopoietic growth fa ctor that has been shown to act synergistically with rhEpo in accelera ting erythropoiesis in vitro. The purpose of this study in a primate m odel was to determine if the administration of rhIL-3 in combination w ith rhEpo could augment the erythropoietic response to acute blood los s more than rhEpo therapy alone. Twenty-four adult male baboons were r andomized into four groups. The induction of acute normovolemic anemia to a hematocrit of 20% was accomplished via exchange-transfusion with 6% hetastarch. The groups were then treated for 7 consecutive days wi th the following growth factors: group I(n=7), no growth factors; grou p II (n=5), rhIL-3 alone (100 mu g/kg/d); group III (n=6), rhEpo alone (1000 U/kg/d); group IV (n=6), rhEpo (1000 U/kg/d) plus rhIL-3 (100 m u g/kg/d). All animals received folate, vitamin B-12, and intravenous iron-dextran immediately following the exchange-transfusion. Response to therapy was monitored for 35 days. There were no adverse reactions following growth factor administration. The analysis of erythropoietic rates between study days I through II, as determined via linear regre ssion analysis, revealed that hematocrits increased significantly fast er in the groups receiving rhEpo compared to controls. The administrat ion of rhIL-3, however, did not increase the rate of erythropoiesis wh en compared to controls, nor did it augment response when added to the rhEpo regimen. The results of this study demonstrate that the adminis tration of rhIL-3 alone had no significant effect on erythropoiesis in this setting of acute blood loss. Further, despite promising in vitro data, rhIL-3 provided no additional stimulation of erythropoiesis in animals receiving rhEpo. Nevertheless, the study confirms that the pha rmacologic acceleration of erythropoiesis by rhEpo alone remains an at tractive alternative to homologous transfusion.