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Effect of granulocyte colony-stimulating factor treatment on ex vivo blood
cytokine response in human volunteers
T Hartung, WD Docke, F Gantner, G Krieger, A Sauer, P Stevens, HD Volk and A Wendel
Department of Biochemical Pharmacology, University of Konstanz, Germany.
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.
Volume 85,
Issue 9,
pp. 2482-2489,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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