Mechanism of the inhibitory action of cyclooxygenase inhibitors on leukocyte infiltration: Involvement of endogenous histamine

Noriyasu Hirasawa, Kazuo Ohuchi, Masako Watanabe, Susumu Tsurifuji

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The mechanism of the inhibitory action of cyclooxygenase inhibitors on leukocyte accumulation in the inflammatory locus was investigated in an allergic inflammation of the air pouch types in rats. Three kinds of cyclooxygenase inhibitors, indomethacin, diclofenac and tiaprofenic acid, caused not only inhibition of the vascular permeability response and leukocyte accumulation but also elevation of histamine levels in the exudate. These effects of indomethacin were all reversed by local administration of prostaglandin E2. Pyrilamine, an H1 antagonist, did not affect the anti-inflammatory actions of indomethacin. The H2 antagonists, cimetidine, ranitidine and famotidine, decreased the inhibitory effect of indomethacin on leukocyte accumulation without affecting the inhibitory action on vascular permeability. These results indicate that the inhibitory action of cyclooxygenase inhibitors on leukocyte accumulation is derived from their blocking effect against generation of PGE2 which works as an inhibitory factor on the production of histamine in the inflammatory tissues.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalEuropean Journal of Pharmacology
Volume144
Issue number3
DOIs
Publication statusPublished - 1987 Dec 15

Keywords

  • Allergic inflammation
  • Cyclooxygenase inhibitors
  • H receptors
  • Histamine
  • Leukocytes

ASJC Scopus subject areas

  • Pharmacology

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