Interleukin‐13 in asthma pathogenesis

Summary: Bronchial asthma is a complex disorder that is thought to arise as a result of aberrant T‐lymphocyte responses to noninfectious environmental antigens. In particular, the symptoms of asthma are closely associated with the presence of activated T‐helper 2 cell (Th2) cytokine‐producing cells [interleukin (IL)‐4, IL‐5, IL‐9, and IL‐13] in the airway wall. Although each of the Th2 cytokines likely contributes to the overall immune response directed against environmental antigens, a substantial body of evidence points to a singular role for IL‐13 in the regulation of the allergic diathesis. Initial studies in animal models of disease provided compelling evidence that IL‐13, independently of other Th2 cytokines, was both necessary and sufficient to induce all features of allergic asthma. The importance of IL‐13 in allergic disorders in humans is supported by consistent associations between tissue IL‐13 levels and genetic variants in the IL‐13 gene with asthma and related traits. With the preponderance of evidence continuing to support a pivotal role for IL‐13 in allergic disorders, attention is now turned toward understanding the mechanisms by which this cytokine may mediate the pathophysiological features of allergic disease. The emerging paradigm is that IL‐13 induces features of the allergic response via a complex array of actions on resident airway cells rather than through traditional effector pathways involving eosinophils and immunoglobulin E‐mediated events. In light of these recent developments, this review explores our current understanding of the singular role of IL‐13 in the pathogenesis of asthma, with a particular focus on new insights into the mechanisms by which IL‐13 mediates various features of asthma.