Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil kinetics and function in normal human volunteers.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) (250 microg/m2) was administered subcutaneously to 7 normal volunteers for up to 14 days to study its effects on neutrophil kinetics and function. With treatment, blood neutrophil counts rose gradually to peak at 3 1/2 times baseline by day 14. At day 5 marrow mitotic cells were increased and post-mitotic cells decreased, and the transit time through the post-mitotic marrow pool accelerated (normal = 6.4 days, GM-CSF = 3.9 days; P < 0.01). Treatment had little effect on the blood neutrophil half-life (normal = 9.6 +/- 1.3 hours; GM-CSF = 13.1 +/- 2.4 hours, P > 0.05); or the neutrophil turnover rate (normal = 78.5 +/- 11.9 x 10(7)/cells/kg/day, GM-CSF = 91.4 +/- 19.8 x 10(7)/cells/kg/day, P > 0.05). GM-CSF reduced the number of neutrophils migrating to skin chambers (normal = 104 +/- 25.0 x 10(6)/cells, GM-CSF = 48.6 +/- 16.0 x 10(6)/cells; P < 0.05). Treatment increased expression of CD11b/CD18 but not Fcgamma receptors (CD16, CD32, CD64). Treatment also stimulated the in vitro neutrophil respiratory burst in response to a variety of agonists, and this enhancement persisted for the duration of treatment. All subjects experienced local and systemic adverse effects and developed eosinophilia. This study indicates that GM-CSF at a dose of 250 microg/m2 causes neutrophilia chiefly by accelerating delivery of neutrophils from the marrow to the blood and by decreasing migration from the blood to the tissues, with only a modest effect on neutrophil production and blood half-life.
Dale
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DC
University of Washington, Seattle and Puget Sound Blood Center, 98195-6422, USA.
Liles
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Llewellyn
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Price
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TH
D000328:Adult; D001853:Bone Marrow / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation; D007958:Leukocyte Count; D019891:Leukopoiesis / Q000187:drug effects; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008165:Luminol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor