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, Volume 28, Issue 1–2, pp 108–114 | Cite as

Prostaglandin E2 prevents diclofenac-induced enhancement of histamine release and inflammation evoked byin vivo challenge with compound 48/80 in the hamster cheek pouch

  • J. Raud
  • A. Sydbom
  • S. -E. Dahlén
  • P. Hedqvist
Inflammation and Immunomodulation

Abstract

Based on observations obtained by the use of intravital microscopy, we report that prostaglandins, (PGs) can exert inhibitory effects on mast cell-dependent inflammation. Thus, the PG-synthesis inhibitors diclofenac and indomethacin potentiated extravasation of plasma evoked by challenge with the mast cell secretagogue compound 48/80. Although the plasma leakage induced by compound 48/80 was in large mediated by histamine, neither diclofenac nor indomethacin potentiated the plasma leakage caused by exogenous histamine. These findings indicated that endogenous PGs inhibited the mast cell-dependent reaction at the level of mediator release. This mode of action was confirmed, as diclofenac was found to enhance thein vivo release of histamine that ensued challenge with compound 48/80. Moreover, the enhancement of the response to compound 48/80 observed after diclofenac treatment was prevented by local administration of PGE2 (30 nM). This inhibition included both the histamine release and the plasma leakage. In addition, diclofenac enhanced the leukocyte emigration after compound 48/80 challenge, and PGE2 reversed also this effect, suggesting that endogenous PGs (e.g. PGE2) also inhibited the release of chemotactic, mediators.

Keywords

Histamine Prostaglandin Indomethacin PGE2 Histamine Release 

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Copyright information

© Birkhäuser Verlag 1989

Authors and Affiliations

  • J. Raud
    • 1
    • 3
  • A. Sydbom
    • 2
  • S. -E. Dahlén
    • 1
    • 3
  • P. Hedqvist
    • 1
    • 3
  1. 1.Department of Physiology IKarolinska InstitutetStockholmSweden
  2. 2.Department of PharmacologyKarolinska InstitutetStockholmSweden
  3. 3.Department of Institute of Environmental MedicineKarolinska InstitutetStockholmSweden

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