The In Vitro Effects of Granulocyte and Granulocyte-Macrophage Colony-Stimulating Factor on Interleukin-3-Dependent Proliferation of Human Neonatal Circulating Progenitor Cells

ABSTRACT: Recombinant human granulocyte (rhG) colony-stimulating factor (CSF) and recombinant human granulocyte-macrophage (rhGM) CSF have been used to enhance neonatal neutrophil host defense. We aimed to determine the comparative efficacy of rhG-CSF and rhGM-CSF in increasing numbers of granuloctye colony-forming unit (CFU-G) and granulocyte-macrophage colony-forming unit (CFU-GM) in recombinant human (rh) IL-3-dependent cultures of human neonatal circulating hematopoietic progenitor cells, including cells from infants born to hypertensive mothers. We also investigated the relationship between fractional increase in CFU-G and endogenous plasma concentraton of G-CSF. Circulating mononuclear cells were harvested from 25 neonates, and standard short-term assays in semisolid agar were established in the presence of rhIL-3 alone, rhIL-3 with rhG-CSF and rhGM-CSF, and both rhG-CSF and rhGM-CSF. CFU-G and CFU-GM were counted on d 14. Total colony number and CFU-G were significantly greater in cultures supplemented with rhG-CSF, with or without rhGM-CSF (p < 0.001 and p < 0.0005 for total colony number and CFU-G, respectively), when compared with cultures with rhIL-3 alone. Progenitor cells from three infants born to hypertensive mothers responded similarly. Total colony numbers and CFU-G were not increased by rhGM-CSF alone or by addition of rhGM-CSF to rhG-CSF; however, the proportions of CFU-GM were (p < 0.05 and p < 0.001, respectively, compared with rhIL-3 alone). Fractional increases in CFU-G with rhG-CSF were independent of plasma concentraton of G-CSF (r = 0.17; 95% confidence interval −0.5 to 0.19; p = 0.35). rhG-CSF was more efficacious than rhGM-CSF in enhancing CFU-G numbers in rhIL-3-dependent cultures, and plasma concentration of G-CSF did not predict response.