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

Abstract

We investigated whether anti-inflammatory effects of treatment with granulocyte colony-stimulating factor (G-CSF, filgrastim) are mediated via prostaglandin E₂ (PGE₂) induction. In a double-blind crossover study, 10 healthy volunteers received 300 μg 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 PGE₂ and thromboxane (TxB₂) release were 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-α or interferon-γ 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 PGE₂ and TxB₂ release. Cyclooxygenase inhibition counteracts neither the hematopoietic nor the anti-inflammatory activity of G-CSF but reduces side effects.