A single dose of granulocyte-macrophage colony-stimulating factor induces systemic interleukin-8 release and neutrophil activation in healthy volunteers.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are frequently used in the clinical management of neutropenia. These cytokines not only enhance the proliferation of myeloid precursor cells but also influence the function of mature leukocytes. In a previous study, we found that the in vivo effects of G-CSF on neutrophils differed from those in vitro. In the present study, we investigated the effects of a single dose of recombinant GM-CSF (7.5 microg/kg, subcutaneously) on neutrophils, eosinophils, and monocytes in healthy volunteers. We analyzed leukocyte kinetics, phenotypical changes, neutrophil degranulation, and systemic cytokine production. After GM-CSF injection, phenotypical changes included upregulation of CD11b on all three cell types and a decreased expression of L-selectin and Fc(gamma)RIII on neutrophils. Neutrophil degranulation was evident from the increased plasma concentrations of lactoferrin and elastase. GM-CSF induced the release of interleukin-8 (IL-8), but not of IL-6 or tumor necrosis factor alpha. In comparison to the results from our previous study with G-CSF in healthy volunteers, GM-CSF induced a stronger activation of mature neutrophils but had a much less pronounced effect on the production and maturation of neutrophil precursors. These data may help to guide the choice between the two cytokines in different clinical situations.
van Pelt
L J
LJ
Emma Children's Hospital, Department of Pediatrics, Amsterdam, The Netherlands.
Huisman
M V
MV
Weening
R S
RS
von dem Borne
A E
AE
Roos
D
D
van Oers
R H
RH
D000328:Adult; D003594:Cytoplasmic Granules / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D007700:Kinetics; D019041:L-Selectin / Q000096:biosynthesis / Q000235:genetics; D007781:Lactoferrin / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D019272:Leukocyte Elastase; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D010196:Pancreatic Elastase / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007781:Lactoferrin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase