Prevention of endotoxemia-induced acute respiratory distress syndrome- like lung injury in rabbits by a monoclonal antibody to IL-8

Kenji Yokoi, Naofumi Mukaida, Akihisa Harada, Yoh Watanabe, Kouji Matsushima

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

We have herein established an endotoxemia-induced acute respiratory distress syndrome (ARDS)-like lung injury model in rabbits and examined the involvement of IL-8 in this condition by using a neutralizing antibody. Rabbits were administered a sublethal dose of lipopolysaccharide (LPS) intravenously 36 hours after the intratracheal instillation of heat-killed Streptococcus pyogenes (OK-432). At 36 hours after OK-432 priming, a mild infiltration into the lungs, consisting of a small number of neutrophils and macrophages, was observed without destruction of pulmonary architecture. A subsequent challenge with a sublethal dose of LPS induced pathologic changes characteristic of ARDS-such as extensive edema in alveolar lumina, marked infiltration composed of a large number of neutrophils and a few macrophages, fibrin deposit in alveolar space, and destruction of pulmonary architecture- resulting in severe hypoxemia. Concomitantly, LPS challenge after priming with OK-432 induced a marked elevation of IL-8 levels in serum and bronchoalveolar lavage fluid with local IL-8 production in lungs, as revealed by immunohistochemical analysis. An anti-IL-8 antibody treatment almost completely prevented pulmonary edema, destruction of pulmonary architecture, and impairment in gas exchange as well as neutrophil infiltration in lungs; there was also a significant reduction in the rate of acute lethality. These results provide evidence that IL-8 has a pivotal role in the induction of ARDS associated with endotoxemia, probably by recruiting and activating neutrophils locally.

Original languageEnglish (US)
Pages (from-to)375-384
Number of pages10
JournalLaboratory Investigation
Volume76
Issue number3
StatePublished - Mar 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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