EFFECT OF GRANULOCYTE-COLONY-STIMULATING FACTOR TREATMENT ON EX-VIVO BLOOD CYTOKINE RESPONSE IN HUMAN VOLUNTEERS

We explored the ex vivo alterations in the cytokine release of stimula ted blood taken from healthy volunteers treated subcutaneously with 48 0 mu g granulocyte colony-stimulating factor (G-CSF). In a double-blin d, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-ind ucible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediato r release was also initiated with muramyl dipeptide, Staphylococcus au reus enterotoxin A, lipoteichoic acid, streptolysin O, complement fact or C5a, phytohemagglutinin, or phorbol myristate acetate. In blood fro m G-CSF-treated subjects, our major findings were (1) a maximal 12-fol d increase in interleukin-l receptor antagonist (IL-1ra) release and a n 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 in terferon-gamma (lFN-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 res ponse. (C) 1995 by The American Society of Hematology.