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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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

Sonja von Aulock, Eva-Maria Boneberg, Isabel Diterich and Thomas Hartung
Journal of Pharmacology and Experimental Therapeutics February 2004, 308 (2) 754-759; DOI: https://doi.org/10.1124/jpet.103.058198
Sonja von Aulock
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Eva-Maria Boneberg
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Isabel Diterich
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Thomas Hartung
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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

  • This study was supported by the German Research Council Grant 324/1 TP2.

  • DOI: 10.1124/jpet.103.058198.

  • 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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Journal of Pharmacology and Experimental Therapeutics: 308 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 308, Issue 2
1 Feb 2004
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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

Sonja von Aulock, Eva-Maria Boneberg, Isabel Diterich and Thomas Hartung
Journal of Pharmacology and Experimental Therapeutics February 1, 2004, 308 (2) 754-759; DOI: https://doi.org/10.1124/jpet.103.058198

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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

Sonja von Aulock, Eva-Maria Boneberg, Isabel Diterich and Thomas Hartung
Journal of Pharmacology and Experimental Therapeutics February 1, 2004, 308 (2) 754-759; DOI: https://doi.org/10.1124/jpet.103.058198
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