gms | German Medical Science

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Deutsche Gesellschaft für Infektiologie,
Deutsche AIDS-Gesellschaft,
Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit,
Paul-Ehrlich-Gesellschaft für Chemotherapie

23.06. - 26.06.2010, Köln

IL-1 receptor antagonist exerts anti-apoptotic and barrier-protective effects towards alveolar epithelium in a murine model of LPS-induced acute lung injury

IL-1 Rezeptor Antagonist wirkt anti-apoptotisch und Alveolarepithel-protektiv im Maus-Modell der LPS-induzierten Acute Lung Injury

Meeting Abstract

  • S. Herold - University of Giessen Lung Center, Department of Internal Medicine, Justus-Liebig-University, Division of Pulmonary and Critical Care Medicine and Infectious Diseases, Giessen, Germany
  • T. Shafiei Tabar - University of Giessen Lung Center, Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany
  • H. Janssen - Hospital of Dueren, Department of Surgery II, Dueren, Germany
  • W.A. Kuziel - Daiichi Sankyo Research Institute, Edison, NY, United States
  • W. Seeger - University of Giessen Lung Center, Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany
  • M. Steinmueller - University of Giessen Lung Center, Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany
  • J. Lohmeyer - University of Giessen Lung Center, Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP44

DOI: 10.3205/10kit100, URN: urn:nbn:de:0183-10kit1006

Published: June 2, 2010

© 2010 Herold et al.
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Outline

Text

Background: Acute lung injury (ALI) is a frequent complication of gram-negative pneumonia and is characterized by high alveolar levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and alveolar barrier dysfunction. However, the contribution of IL-1β to epithelial injury progression and the role of the endogenous IL-1β antagonist IL-1ra (IL-1 receptor antagonist) and its potential therapeutic value in pathogen-induced acute lung injury has not been investigated.

Methods and results:Intratracheal LPS instillation into C57BL/6 mice induced elevated levels of IL-1β in bronchoalveolar lavage fluid (BALF), significant alveolar epithelial cell (AEC) apoptosis and pronounced loss of lung barrier function in terms of alveolar albumin leakage, together with sustained recruitment of neutrophils and, lateron, of exudate macrophages into the alveolar air space. Concomitantly, IL-1ra mRNA was found highly upregulated in FACS-separated alveolar recruited CCR2+ exudate macrophages compared to peripheral blood monocytes and was detected at high levels in BALF at 48h post LPS challenge when exudate macrophages were numerously present in the alveoli. Blockade of CCR2+ exudate macrophage recruitment to the lung in CCR2-deficient mice was associated with enhanced AEC apoptosis and alveolar barrier dysfunction after LPS treatment. Interestingly, alveolar IL-1ra release was widely reduced in CCR2-deficient mice compared to wild-type mice upon LPS challenge. Systemic or local alveolar treatment of LPS-challenged CCR2-/- mice with recombinant IL-1ra in turn resulted in attenuated AEC apoptosis and preserved barrier function.

Conclusion: CCR2+ exudate macrophages exert anti-apoptotic, barrier-protective effects towards alveolar epithelial cells by expression of IL-1ra in a mouse model of LPS-induced ALI. Furthermore, these data suggest IL-1ra application to be a potential treatment strategy for severe bacterial pneumonia.