The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Sep 2009
ReviewGenetics and pharmacogenetics of the leukotriene pathway.
Leukotrienes are now established contributors to the inflammatory process in asthma, and leukotriene modifiers are mainstays in the therapy of asthma. This review focuses on published association studies implicating the role of leukotriene pathway genes in asthma pathogenesis and treatment response, specifically focusing on those genetic variants associated with asthma affection status, the development of aspirin-exacerbated respiratory disease, and pharmacogenetic response. ⋯ Despite these successes, genetic investigations into this pathway remain in their formative stages. Future studies aimed at providing a broader scope of investigation through increased sample sizes and through genome-wide approaches are needed.
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J. Allergy Clin. Immunol. · Sep 2009
Comparative StudyDistinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese.
Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is reported to be different in inflammatory patterns of the sinonasal mucosa in white patients. Studies in nonwhite populations may further be helpful to understand the pathogenic mechanisms of CRS. ⋯ Both Chinese CRSsNP and CRSwNP patients demonstrate impaired regulatory T cell function and enhanced T(H)1/T(H)2/T(H)17 responses. CRSsNP is confirmed to be a predominant T(H)1 milieu, whereas T(H)2 skewed inflammation with predominant T(H)17 reactions, and infiltration of natural killer T cells can be demonstrated only in eosinophilic CRSwNP, but not in noneosinophilic CRSwNP.
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J. Allergy Clin. Immunol. · Sep 2009
Eosinophil-derived IFN-gamma induces airway hyperresponsiveness and lung inflammation in the absence of lymphocytes.
Eosinophils are key players in T(H)2-driven pathologies, such as allergic lung inflammation. After IL-5- and eotaxin-mediated tissue recruitment, they release several cytotoxic and inflammatory mediators. However, their exact contribution to asthma remains controversial. Indeed, in human subjects anti-IL-5 treatment inhibits eosinophilia but not antigen-induced airway hyperresponsiveness (AHR). Likewise, lung fibrosis is abrogated in 2 strains of eosinophil-deficient mice, whereas AHR is inhibited in only one of them. Finally, eosinophils have been shown to attract T(H)2 lymphocytes at the inflammatory site. ⋯ These results support the important and previously unsuspected contribution of eosinophils to lung inflammation independently of lymphocytes through production of IFN-gamma, the prototypical T(H)1 cytokine.