In adults, recombinant Erythropoietin (rEpo) stimulates erythropoiesis but it does not diminish granulocytopoiesis. If pluripotent progenitors are severely limited, however, rEpo can diminish granulocytopoiesis. For instance, newborn rats (small pluripotent progenitor pool/gm body wt) treated with very high doses of rEpo develop hyporegenerative neutropenia (Blood 78:124,1991), and human fetal progenitors exposed to very high concentrations of rEpo have decreased granulocytopoiesis in vitro (Am J Hematol 39:108,1992). Administration of rG-CSF is currently being tested as a potential treatment for neutropenia in neonates, but it is not clear whether high concentrations of rG-CSF might diminish erythropoiesis in this population. To assess this possibility, we added increasing concentrations of rG-CSF, in vitro, to progenitors obtained from the bone marrow and liver of five human fetuses, 13-22 weeks gestation, and the umbilical cord blood of five term and five preterm infants. Progenitors were cultured in rG-CSF concentrations of either zero, 0.1 ng/mL or 10.0 ng/mL. Cultures for primitive erythroid progenitors (BFU-E) contained 20 U rEpo and 10 ng rSCF/mL, those for mature erythroid progenitors (CFU-E) contained 1U rEpo/mL. In all samples tested, the inclusion of rG-CSF in the cultures did not result in a diminution in colonies generated from BFU-E or CFU-E, nor did rG-CSF result in fewer normoblasts per erythroid colony. For instance, fetal bone marrow produced 8.6± 1.8 BFU-E colonies/104 cells when cultured in zero G-CSF vs. 9.4±2.6 BFU-E colonies/104 cells plated in 10.0 ng G-CSF/mL (X±SEM,p=0.80); fetal liver produced 37.0± 5.0 BFU-E/104 cells in zero G-CSF vs. 29.0±3.0 BFU-E/104 cells cultured in 10 ng G-CSF/mL (p = 0.75); term cord blood produced 13.0±2.2 BFU-E/104 cells in zero G-CSF vs. 17.5± 1.9 BFU-E/104 cells plated in 10 ng/mL G-CSF (p = 0.19); preterm cord blood produced 12.7± 1.5 BFU-E/104 cells in zero G-CSF vs. 19.0±1.9 BFU-E/104 cells plated in 10 ng G-CSF/mL (p =0.23). Fetal bone marrow produced 1.6×105 normoblasts/BFU-E colony when cultured in zero G-CSF vs. 1.9×105 normoblasts/BFU-E colony when plated with 10 ng/mL of G-CSF. On the basis of these studies we predict that administration of rG-CSF to preterm infants is not likely to result in a down-modulation of erythropoiesis.
