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.
Footnotes
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This study was supported by the German Research Council Grant 324/1 TP2.
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DOI: 10.1124/jpet.103.058198.
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ABBREVIATIONS: G-CSF, granulocyte colony-stimulating factor; IL, interleukin; TNFα, tumor necrosis factor-α; IFNγ, interferon-γ; LPS, lipopolysaccharide; PG, prostaglandin; NSAID, nonsteroidal anti-inflammatory drug; COX, cyclooxygenase; TxB2, thromboxane B2; LTB4, leukotriene B4; U46.619, 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α.
- Received August 5, 2003.
- Accepted November 7, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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