Granulocyte colony-stimulating factor (filgrastim) treatment primes for increased ex vivo inducible prostanoid release.
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 microg 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 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-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 PGE(2) and TxB(2) release. Cyclooxygenase inhibition counteracts neither the hematopoietic nor the anti-inflammatory activity of G-CSF but reduces side effects.
von Aulock
Sonja
S
Biochemical Pharmacology, University of Konstanz, Germany.
Boneberg
Eva-Maria
EM
Diterich
Isabel
I
Hartung
Thomas
T
D000328:Adult; D015232:Dinoprostone / Q000378:metabolism; D004311:Double-Blind Method; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011994:Recombinant Proteins; D013929:Thromboxane B2 / Q000378:metabolism
D011453:Prostaglandins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000069585:Filgrastim