Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions
1999
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
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