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Interleukin-13: prospects for new treatments.

ABSTRACT: IL-13 is a T-helper type 2 cytokine. Animal models have implicated IL-13 as a critical cytokine in the development of asthma and chronic obstructive pulmonary disease (COPD). In vitro IL-13 exerts important effects on both structural and inflammatory cells within the airway and has the capacity to drive the clinical features of airways disease. In asthma, this view is strongly supported by associations with IL-13 genetic polymorphisms and increased mRNA and protein expression in blood, sputum and bronchial submucosa. In particular, IL-13 up-regulation is associated with severe disease. Current evidence in COPD is conflicting, with some reports supporting and others refuting a role for IL-13. Early clinical trials of anti-IL-13 therapies in asthma have shown promise, and the results of further efficacy studies are eagerly awaited.

SUBMITTER: Brightling CE

PROVIDER: S-EPMC3992377 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Interleukin-13: prospects for new treatments.

Brightling C E CE Saha S S Hollins F F

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20091030 1

IL-13 is a T-helper type 2 cytokine. Animal models have implicated IL-13 as a critical cytokine in the development of asthma and chronic obstructive pulmonary disease (COPD). In vitro IL-13 exerts important effects on both structural and inflammatory cells within the airway and has the capacity to drive the clinical features of airways disease. In asthma, this view is strongly supported by associations with IL-13 genetic polymorphisms and increased mRNA and protein expression in blood, sputum an ...[more]

PMID: 19878194

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Project description:Asthma is characterized by episodic, reversible airflow obstruction associated with variable levels of inflammation. Over the past several decades, there has been an increasing appreciation that the clinical presentation of asthma comprises a diverse set of underlying pathologies. Rather than being viewed as a single disease entity, asthma is now thought of as a clinical syndrome with the involvement of multiple pathological mechanisms. While it is appreciated that eosinophilia is present in only a subset of patients, it remains a key feature of asthma and other eosinophilic disorders such as atopic dermatitis, eosinophilic esophagitis, and chronic rhinosinusitis with nasal polyps. Eosinophils are bone marrow-derived leukocytes present in low numbers in health; however, during disease the type 2 cytokines [interleukins (IL)-4, -5, and -13] can induce rapid eosinophilopoiesis, prolonged eosinophil survival, and trafficking to the site of injury. In diseases such as allergic asthma there is an aberrant inflammatory response leading to eosinophilia, tissue damage, and airway pathology. IL-13 is a pleiotropic type 2 cytokine that has been shown to be integral in the pathogenesis of asthma and other eosinophilic disorders. IL-13 levels are elevated in animal models of eosinophilic inflammation and in the blood and tissue of patients diagnosed with eosinophilic disorders. IL-13 signaling elicits many pathogenic mechanisms including the promotion of eosinophil survival, activation, and trafficking. Data from preclinical models and clinical trials of IL-13 inhibitors in patients have revealed mechanistic insights into the role of this cytokine in driving eosinophilia. Promising results from clinical trials further support a key mechanistic role of IL-13 in asthma and other eosinophilic disorders. Here, we provide a perspective on the role of IL-13 in asthma and other eosinophilic disorders and describe ongoing clinical trials targeting this pathway in patients with significant unmet medical needs.

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Interleukin-13: prospects for new treatments.

Publications

Interleukin-13: prospects for new treatments.

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