Interferon-γ , Pulmonary Macrophages and Airway Responsiveness in Asthma

Author(s): Rakesh K. Kumar, Ming Yang, Cristan Herbert, Paul S. Foster.

Journal Name: Inflammation & Allergy - Drug Targets (Discontinued)

Volume 11 , Issue 4 , 2012

Abstract:

Asthma is increasingly being recognised as involving not only allergic inflammatory mechanisms but also a variety of other cell types and cytokines. While the role of interferon-γ(IFN-γ) in asthma remains controversial, it has been proposed to contribute to the pathogenesis of both chronic stable asthma and acute severe asthma. We have shown that in a model of chronic allergic asthma in mice, airway hyper-responsiveness (AHR) is independent of various Th2 cytokines and their signalling pathways, but is dependent on IFN-γ. In a model of an allergen-induced acute exacerbation of chronic asthma, we have demonstrated that activation of pulmonary macrophages may play a critical role in driving the inflammatory response. Furthermore, we have demonstrated that IFN-γstimulation of macrophages can lead to steroidresistant airway inflammation and AHR via the production of interleukin-27. These findings strengthen the notion that the pathogenesis of the lesions of asthma, and especially of AHR, involves both Th2 and Th1 cytokines, as well as interaction between the allergic response and the innate host defence system. Targeting the effects of IFN-γon pulmonary macrophages may be particularly relevant to the treatment of steroid-resistant acute exacerbations of asthma.

Keywords: Acute exacerbation, airway hyperresponsiveness, asthma, interferon-γ, pulmonary macrophages, Th1 and Th2 cytokines, Asthma, airway hyper-responsiveness (AHR), interleukin-27, innate host defence system

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2012
Page: [292 - 297]
Pages: 6
DOI: 10.2174/187152812800958951
Price: $58

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