title: Effects of recombinant human erythropoietin and interleukin-3 on erythropoietic recovery from acute anemia.
abstract: The risks inherent in the use of homologous blood products have increased efforts toward identifying alternatives to transfusion. We have previously shown that the administration of recombinant human erythropoietin (rhEpo) enhances the erythropoietic response to acute blood loss. Recombinant human interleukin-3 (rh-IL-3) is a hematopoietic growth factor that has been shown to act synergistically with rhEpo in accelerating erythropoiesis in vitro. The purpose of this study in a primate model was to determine if the administration of rhIL-3 in combination with rhEpo could augment the erythropoietic response to acute blood loss more than rhEpo therapy alone. Twenty-four adult male baboons were randomized 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 with the following growth factors: group I (n = 7), no growth factors; group II (n = 5), rhIL-3 alone (100 micrograms/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 micrograms/kg/d). All animals received folate, vitamin B12, 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 1 through 11, as determined via linear regression analysis, revealed that hematocrits increased significantly faster in the groups receiving rhEpo compared to controls. The administration of rhIL-3, however, did not increase the rate of erythropoiesis when compared to controls, nor did it augment response when added to the rhEpo regimen. The results of this study demonstrate that the administration 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 pharmacologic acceleration of erythropoiesis by rhEpo alone remains an attractive alternative to homologous transfusion.
authors.affiliation: Department of Surgery, Michael Reese Medical Center, University of Illinois at Chicago.
authors.forename: B S
authors.initials: BS
authors.lastname: Rosen
authors.forename: E A
authors.initials: EA
authors.lastname: Levine
authors.forename: J C
authors.initials: JC
authors.lastname: Egrie
authors.forename: L R
authors.initials: LR
authors.lastname: Sehgal
authors.forename: R
authors.initials: R
authors.lastname: Greenberg
authors.forename: A L
authors.initials: AL
authors.lastname: Rosen
authors.forename: H D
authors.initials: HD
authors.lastname: Levine
authors.forename: S A
authors.initials: SA
authors.lastname: Gould
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000740:Anemia / Q000097:blood* / Q000188:drug therapy; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D007377:Interleukin-3 / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010215:Papio; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin