Granulocyte Colony-Stimulating Factor(Filgrastim) Treatment Primes for Increased ev Vivo Inducible Prostanoid Release

摘要

We investigated whether anti-inflammatory effects of treatment with granulocyte colony-stimulating factor (G-CSF,filgrastim) are mediated via prostaglandin E_2 (PGE_2) induction.In a double-blind crossover study,10 healthy volunteers received 300 mug of filgrastim or saline 1 week apart.This was repeated after oral administration of 50 mg of flurbiprofen 1 h before injection.The increase in neutrophilic granulocytes initiated by G-CSF was augmented significantly by flurbiprofen.Lipopolysaccharide-induced PGE_2 and thromboxane (TxB_2) release when increased 8 h after G-CSF treatment.This increase was abrogated by flurbiprofen.However,flurbiprofen did not affect G-CSF-mediated decrease in tumor necrosis factor-alpha or interferon-gamma release.Of the volunteers treated with G-CSF,eight reported side effects (headache and bone pain) against none in the saline group.When flurbiprofen was given before injection,one volunteer each reported side effects in the G-CSF and in the saline group.These data show that G-CSF primes for increased PEG_2 and TxB_2 release.Cyclooxygenase inhibition counteracts neither the hematopoietic nor the anti-inflammatory activity of G-CSF but reduces side effects.