title: Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-gamma.
abstract: In a double-blind, placebo-controlled, randomized study, 10 healthy men received either a single dose of 480 microg granulocyte colony-stimulating factor (G-CSF) or saline. Blood taken from the volunteers was stimulated with 10 microg/mL endotoxin and released cytokines were measured by enzyme-linked immunosorbent assay. Expression of G-CSF receptors on leukocytes was examined by flow cytometry and reverse transcriptase-polymerase chain reaction. Functional activity of these receptors was tested by challenging isolated leukocyte populations to release cytokines with endotoxin in the presence of G-CSF. The G-CSF treatment attenuated the release of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-1beta, and interferon (IFN)-gamma in ex vivo lipopolysaccharide (LPS)-stimulated whole blood. In blood from untreated volunteers the presence of G-CSF in vitro also attenuated the LPS-stimulated release of these cytokines. G-CSF in vitro also attenuated TNF-alpha release from elutriation-purified monocytes. In the presence of 10 ng/mL recombinant TNF-alpha, the attenuation of LPS-inducible IFN-gamma release by G-CSF was blunted in whole blood. However, G-CSF had no such effect on IFN-gamma release from isolated lymphocytes stimulated with anti-CD3 or a combination of TNF-alpha and IL-12. G-CSF receptor expression was detected in human neutrophils and monocytes but not in lymphocytes by means of RT-PCR as well as flow cytometry. These results indicate that G-CSF receptors expressed on monocytes are functional in modulating monokine release. We conclude that the attenuation of IFN-gamma release from lymphocytes is not a direct effect of G-CSF on these cells but is rather due to the inhibition of monocytic IL-12 and TNF-alpha release by G-CSF. (Blood. 2000;95:270-276)
authors.affiliation: University of Konstanz, Biochemical Pharmacology, Konstanz, Germany.
authors.forename: E M
authors.initials: EM
authors.lastname: Boneberg
authors.forename: L
authors.initials: L
authors.lastname: Hareng
authors.forename: F
authors.initials: F
authors.lastname: Gantner
authors.forename: A
authors.initials: A
authors.lastname: Wendel
authors.forename: T
authors.initials: T
authors.lastname: Hartung
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D000069585:Filgrastim; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D015846:Monokines / Q000096:biosynthesis* / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010919:Placebos; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D011994:Recombinant Proteins; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008070:Lipopolysaccharides; D015846:Monokines; D010919:Placebos; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D000069585:Filgrastim