Role of IL-18 in second-Hand Smoke-induced emphysema

Adelheid Kratzer, Jonas Salys, Claudia Nold-Petry, Carlyne D Cool, Martin Zamora, Russ Bowler, Andreas Rembert Koczulla, Sabina Janciauskiene, Michael G. Edwards, Charles A Dinarello, Laimute Taraseviciene-Stewart

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

Chronic second-hand smoke (SHS) exposure comprises the main risk factor for nonsmokers to develop chronic obstructive pulmonary disease (COPD). However, the mechanisms behind the chronic inflammation and lung destruction remain incompletely understood. In this study, we show that chronic exposure of Sprague-Dawley rats to SHS results in a significant increase of proinflammatory cytokine IL-18 and chemokine (C-C motif) ligand 5 in the bronchoalveolar lavage fluid (BALF) and a significant decrease of vascular endothelial growth factor (VEGF) in the lung tissue. SHS exposure resulted in progressive alveolar airspace enlargement, cell death, pulmonary vessel loss, vessel muscularization, collagen deposition, and right ventricular hypertrophy. Alveolar macrophages displayed a foamy phenotype and a decreased expression of the natural inhibitor of IL-18, namely, IL-18 binding protein (IL-18BP).Moreover, IL-18 down-regulated the expression of VEGF receptor-1 and VEGFR receptor-2, and induced apoptosis in pulmonary microvascular endothelial cells in vitro.Wealso observed a trend toward increased concentrations of IL-18 in the BALF of patients with COPD. Our findings suggest that IL-18-mediated endothelial cell death may contribute to vascular destruction and disappearance in SHS-induced COPD. Moreover, IL-18 and IL-18BP are potential new targets for therapeutics. 

Original languageEnglish
Pages (from-to)725-732
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume48
Issue number6
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Keywords

  • Emphysema
  • Inflammation
  • Macrophages
  • Second-hand cigarette smoke
  • Vasculature

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