Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2013 (2013), Article ID 250938, 10 pages
Research Article

Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

Department of Pathology, Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia

Received 8 February 2013; Revised 23 April 2013; Accepted 29 April 2013

Academic Editor: Carlo Jose Freire de Oliveira

Copyright © 2013 Melissa M. Bunting et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.