Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions.
Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 microg 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-alpha), interleukin-12 (IL-12), and interferon gamma (IFN-gamma) 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-gamma and TNF-alpha 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.
Hartung
T
T
Department of Biochemical Pharmacology, University of Konstanz, Germany.
Doecke
W D
WD
Bundschuh
D
D
Foote
M A
MA
Gantner
F
F
Hermann
C
C
Lenz
A
A
Milwee
S
S
Rich
B
B
Simon
B
B
Volk
H D
HD
von Aulock
S
S
Wendel
A
A
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects*; D004311:Double-Blind Method; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000187:drug effects; D018664:Interleukin-12 / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000187:drug effects; D011994:Recombinant Proteins; D012016:Reference Values; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D016207:Cytokines; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D007371:Interferon-gamma; D000069585:Filgrastim