Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 250938, 10 pages http://dx.doi.org/10.1155/2013/250938 Research Article Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma Melissa M. Bunting, Alexander M. Shadie, Rylie P. Flesher, Valentina Nikiforova, Linda Garthwaite, Nicodemus Tedla, Cristan Herbert, and Rakesh K. Kumar Department of Pathology, Infammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia Correspondence should be addressed to Rakesh K. Kumar; r.kumar@unsw.edu.au 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. Tis 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 infammation 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 infammation and then received a single moderate-level challenge to trigger acute airway infammation simulating an asthmatic exacerbation. Te infammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the efect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited signifcantly enhanced expression of markers of alternative activation, together with enhanced expression of proinfammatory 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 signifcantly decreased both airway infammation and the expression of proinfammatory 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 infammation. 1. Introduction Asthma is one of the most common chronic diseases afect- ing children and young adults, especially in economically developed nations. Acute exacerbations of asthma account for a large fraction of the health care costs and morbidity of this illness [1]. Most childhood asthma is allergic, and children hospitalized for severe asthma exacerbations are typically markedly atopic [2]. Exacerbations are characterized by increased airway infammation, which extends further distally [3] and is associated with recruitment of both eosinophils and signifcant numbers of neutrophils [4, 5]. In parallel, patients develop worsening airfow obstruction and its consequences, which may be difcult to manage and can be life threatening [6, 7]. Although usually triggered by viruses, exposure to high levels of allergens is synergistic in the induction of acute exacerbations [8, 9]. Furthermore, these factors appear to converge on a “fnal common path- way” in which the allergic infammatory response, including bystander aeroallergens, may be enhanced as a consequence of the infection [10–12]. However, the cellular and molec- ular events underlying these changes remain incompletely defned. To investigate pathogenetic mechanisms of asthmatic exacerbations, we have developed a model of acute-on- chronic asthmatic infammation of the airways [13]. Tis is based on our well-characterized model of chronic asthma in BALB/c mice, which are systemically sensitized to ovalbumin (OVA) and repeatedly challenged with a low mass concen- tration (≈3 mg/m 3 ) of aerosolized OVA for 4 weeks. Tese