Review of G-CSF and GM-CSF. Effects on neonatal neutrophil kinetics

Abstract

Granulocyte-macrophage (GM-CSF) and granulocyte (G-CSF) colony-stimulating factors support proliferation and differentiation of hematopoietic cells of various lineages. Recombinant human (rh) GM-CSF and rh-G-CSF have been demonstrated in adults to regulate hematopoietic neutrophil progenitor colony growth, stimulate the release of adult bone marrow neutrophil storage pools, and prime adult mature effector function including chemotaxis, oxidative metabolism, phagocytosis, C3bi receptor expression, and antibody-dependent cellular cytotoxicity. To determine their biological activity in the newborn, we examined the effect of rh-GM-CSF in priming neonatal (cord) polymorphonuclear leukocyte (PMN) chemotaxis and superoxide release and of rh-G-CSF and rh-GM-CSF on neonatal bone marrow neutrophil egress in the neonatal rat. A time response (5-120 min) of 100 pmol/L rh-GM-CSF revealed enhanced PMN O2 release, maximal response occurring at 30-60 min (140-150%) (p less than or equal to 0.006). Chemotaxis was also enhanced by 100 pmol/L rh-GM-CSF with an earlier maximal response (5 min) than seen with superoxide release (115% vs. control) (p less than or equal to 0.025). Additionally, 1.5, 3.0, and 5.0 micrograms/kg of rh-G-CSF and rh-GM-CSF given intraperitoneally to newborn Sprague-Dawley rats demonstrated a significant increase of the white blood cell count at 6, 24, and 48 h (p less than or equal to 0.003, less than or equal to 0.008, and less than or equal to 0.0005, respectively) and significant neutrophilia at 6 h (p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)