Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8

Akito Nishimura, Tohru Akahoshi, Michio Takahashi, Kenji Takagishi, Moritoshi Itoman, Hirobumi Kondo, Yuichi Takahashi, Kenji Yokoi, Naofumi Mukaida, Kouji Matsushima

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Accumulating evidence implicates interleukin-8 (IL-8) as an essential mediator in neutrophil-mediated acute inflammation. Neutrophils have also been shown to have a crucial rule in the pathogenesis of acute gouty arthritis. Thus, we investigate the pathophysiological role of IL-8 in an experimental model of acute gout, monosodium urate (MSU) crystal-induced arthritis in rabbits. The injection of MSU crystals into knee jointS caused a marked swelling of jointS. Concomitantly, the infiltration of leukocytes, mostly neutrophils, was observed in synovial membrane and synovial fluids. The injection of MSU crystals also induced an elevation in synovial fluid IL- 8 levels preceding neutrophil infiltration into synovial fluids, without an accompanying increase in plasma IL-8 levels. Immunoreactive IL-8 protein was detected in synovial lining cells at 12-24 h after the injection. IL-8 protein was also observed in infiltrated leukocytes in synovium as early as 3-24 h after the injection. Finally, the intraarticular injection of a neutralizing anti-IL-8 antibody significantly attenuated the crystal-induced joint swelling that occurred at 12 h, and neutrophil infiltration into arthritic joints at 12 and 24 h after the induction. These results provide evidence on the pathogenic roles of locally produced IL-8 in MSU crystal- induced gouty arthritis.

Original languageEnglish (US)
Pages (from-to)444-449
Number of pages6
JournalJournal of Leukocyte Biology
Volume62
Issue number4
DOIs
StatePublished - Oct 1997

Keywords

  • Acute gout
  • MSU crystals
  • Neutrophils

ASJC Scopus subject areas

  • Cell Biology

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