TY - JOUR
T1 - Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions
AU - Hartung, Thomas
AU - Doecke, Wolf Dietrich
AU - Bundschuh, Daniela
AU - Foote, Mary Ann
AU - Gantner, Florian
AU - Hermann, Corinna
AU - Lenz, Andre
AU - Milwee, Steven
AU - Rich, Bill
AU - Simon, Bernadett
AU - Volk, Hans Dieter
AU - Von Aulock, Sonja
AU - Wendel, Albrecht
PY - 1999
Y1 - 1999
N2 - Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 μg filgrastim (recombinant methionyl human granulocyte colony- stimulating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and interferon gamma (IFN-γ) release by whole blood in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added in vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-γ and TNF-α release, suggesting that the anti- inflammatory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphocyte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgrastim induced doubling of all T-cell populations by day 8. Filgrastim decreased proinflammatory cytokine production and lymphocyte proliferation ex vivo throughout prolonged treatment at all doses. This indicates that endogenous granulocyte colony-stimulating factor may counterregulate the inflammatory cytokine cascade and implies a potential indication for filgrastim in chronic inflammatory conditions.
AB - Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 μg filgrastim (recombinant methionyl human granulocyte colony- stimulating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and interferon gamma (IFN-γ) release by whole blood in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added in vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-γ and TNF-α release, suggesting that the anti- inflammatory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphocyte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgrastim induced doubling of all T-cell populations by day 8. Filgrastim decreased proinflammatory cytokine production and lymphocyte proliferation ex vivo throughout prolonged treatment at all doses. This indicates that endogenous granulocyte colony-stimulating factor may counterregulate the inflammatory cytokine cascade and implies a potential indication for filgrastim in chronic inflammatory conditions.
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U2 - 10.1053/cp.1999.v66.a101210
DO - 10.1053/cp.1999.v66.a101210
M3 - Article
C2 - 10546926
AN - SCOPUS:0032717657
SN - 0009-9236
VL - 66
SP - 415
EP - 424
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 4
ER -