BackgroundRepeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM).Methodology/Principal FindingsMice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (RL) and dynamic compliance (Cdyn). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05) the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05) the increase in baseline RL and the decrease in baseline Cdyn caused by chronic exposure to inhaled HDM.Conclusions/SignificanceThese data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.

JH and MG carried out experiments, participated in the experimental design and in the interpretation of data and write the manuscript. KT and RP provided the monoclonal antibody (CA154_582) and revised the manuscript critically. LM, GP and NR did take part to bench work. JMF initiated the project and revised the manuscript. AN did take part to study design and revised the manuscript critically. DC initiated and supervised the "This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org" whole project, was responsible to find grants, participated in the design of the study, reviewed results and reviewed and finalized the manuscript. Conclusions: These data demonstrate that an inhaled anti-IL-13 significantly reduces airway inflammation, hyperresponsiveness and remodeling. Specific neutralization of IL-13 in the lungs using an inhaled anti-IL-13 could represent a novel and effective therapy for the treatment of asthma. Source of support

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