title: Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers.
abstract: We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.
authors.affiliation: Department of Biochemical Pharmacology, University of Konstanz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hartung
authors.forename: W D
authors.initials: WD
authors.lastname: Döcke
authors.forename: F
authors.initials: F
authors.lastname: Gantner
authors.forename: G
authors.initials: G
authors.lastname: Krieger
authors.forename: A
authors.initials: A
authors.lastname: Sauer
authors.forename: P
authors.initials: P
authors.lastname: Stevens
authors.forename: H D
authors.initials: HD
authors.lastname: Volk
authors.forename: A
authors.initials: A
authors.lastname: Wendel
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000328:Adult; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D013682:Teichoic Acids / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D016179:Granulocyte Colony-Stimulating Factor; C026066:enterotoxin A, Staphylococcal; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C009900:lipoteichoic acid