Role of Interleukin-13 in Asthma

Interleukin-13 is a pleiotropic TH2 cytokine that has been shown to be central to the pathogenesis of asthma. Some of the most prominent of the effects of IL-13 include increases in goblet cell differentiation, activation of fibroblasts, elevation of bronchial hyperresponsiveness, and switching of B cell antibody production from IgM to IgE. The relevances of these effects to asthma have been carefully studied in both animal models and more recently in human studies. As the role of IL-13 in asthma has become more defined, a number of potential biomarkers for TH2 airway inflammation, and hence IL-13 activity, have been identified, including blood and sputum eosinophils, total serum IgE, proteins derived from the bronchial epithelium (e.g., serum periostin), and exhaled nitric oxide. Most importantly, many of these markers for TH2 inflammation are strong predictors for positive responses to inhaled corticosteroid treatment. These biomarkers may also be useful in identifying patients who are most likely to benefit from specific IL-13 antagonism, as was demonstrated in a recent clinical trial of anti-IL-13 antibody therapy (lebrikizumab) in patients with poorly controlled asthma despite using inhaled corticosteroids. In that study, significant improvements in FEV1 were observed in patients with elevations of serum periostin but not in patients with normal periostin levels. These data indicate that IL-13 antagonists may fulfill an important unmet need in patients with poorly controlled asthma and biologic evidence of persistent IL-13 activity.