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Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions
Author(s) -
Hartung Thomas,
Doecke WolfDietrich,
Bundschuh Daniela,
Foote MaryAnn,
Gantner Florian,
Hermann Corinna,
Lenz Andre,
Milwee Steven,
Rich Bill,
Simon Bernadett,
Volk HansDieter,
Aulock Sonja,
Wendel Albrecht
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1053/cp.1999.v66.a101210
Subject(s) - filgrastim , granulocyte colony stimulating factor , cytokine , ex vivo , medicine , immunology , tumor necrosis factor alpha , proinflammatory cytokine , pharmacology , granulocyte , lipopolysaccharide , lymphocyte , in vivo , granulocyte macrophage colony stimulating factor , inflammation , biology , chemotherapy , microbiology and biotechnology
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. Clinical Pharmacology & Therapeutics (1999) 66 , 415–424; doi: 10.1053/cp.1999.v66.a101210