THE IN-VITRO EFFECTS OF GRANULOCYTE AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ON INTERLEUKIN-3-DEPENDENT PROLIFERATION OF HUMAN NEONATAL CIRCULATING PROGENITOR CELLS

Recombinant human granulocyte (rhG) colony-stimulating factor (CSF) an d recombinant human granulocyte-macrophage (rhGM) CSF have been used t o 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 col ony-forming unit (CFU-GM) in recombinant human (rh) IL-3-dependent cul tures of human neonatal circulating hematopoietic progenitor cells, in cluding cells from infants born to hypertensive mothers. We also inves tigated the relationship between fractional increase in CFU-G and endo genous plasma concentraton of G-CSF. Circulating mononuclear cells wer e harvested from 25 neonates, and standard short-term assays in semiso lid 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 significantl y 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, respe ctively), when compared with cultures with rhIL-3 alone. Progenitor ce lls from three infants born to hypertensive mothers responded similarl y. 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 CF U-GM were (p < 0.05 and p < 0.001, respectively, compared with rhIL-S 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 enha ncing CFU-G numbers in rhIL-3-dependent cultures, and plasma concentra tion of G-CSF did not predict response.