Interleukin 13 (IL-13) is a cytokine increasingly recognised for novel roles in allergic and other inflammatory conditions. Like many components of the immune response, IL-13 has a physiological role in fighting infection—that is, eliminating helminthic parasites from the intestine—but it also can exert pathological effects when excessively produced. IL-13 has been cited as a component of different types of mucosal inflammation, including allergic asthma, ulcerative colitis, eosinophilic oesophagitis (EO) and several diseases with an important component of fibrosis. Currently, there is a large effort to test anti-IL-13 strategies in the clinic, mostly driven by the proposed role of IL-13 in asthma but also by the discovery of its contribution to other diseases.
As a component of the gut mucosal immune response, IL-13 has been recognised primarily for its role in the inflammatory reaction to helminthic infections. IL-13 works at a number of levels to combat this infection, stimulating mucus production from goblet cells, inducing local eotaxin release to attract eosinophils and increasing IgE production (all responses resembling IL-13 induced airway pathology in experimental allergic asthma), as well as possibly contributing to increased gut motility and epithelial secretion (via disruption of the tight junction and possibly enhanced cystic fibrosis transmembrane conductance regulator mediated apical chloride secretion.
The prominent role of IL-13 in allergic asthma models and excess IL-13 production in human asthma are currently driving the development and testing of anti-IL-13 compounds in clinical trials. Animal models of allergic asthma clearly show that IL-13 unresponsive mice are resistant to allergen induced airway hyperresponsiveness and the ensuing inflammatory changes. Now that early reports support the efficacy of anti-IL-13 antibodies for human asthma, other conditions that implicate IL-13 in their pathogenesis may also benefit from this drug pipeline. For example, IL-13 may be an effector cytokine in fibrotic diseases, from idiopathic pulmonary arterial hypertension to progressive systemic sclerosis. Below we review the association of IL-13 with several gastrointestinal inflammatory diseases, ulcerative colitis, EO and the fibrosis associated with Crohn’s fistulous disease.
IL-13 is a pleiotropic cytokine both in its cellular sources and in its observed actions. Preclinical and in vitro data point to the involvement of this cytokine in the pathogenesis of chronic inflammatory disorders of the gastrointestinal tract, particularly ulcerative colitis, EO and perianal fistula formation in Crohn’s disease. Numerous compounds are available for neutralising IL-13 and activation of its receptor system, of which some have shown biological activity and efficacy in asthma. The study results from anti-IL-13 studies in ulcerative colitis, Crohn’s disease and eventually EO are eagerly awaited to further understand the importance of IL-13 in supporting established inflammation of the gastrointestinal tract.
SOURCE: Mannon P, Reinisch W.Interleukin 13 and its role in gut defence and inflammation. Gut 2012;61:1765-1773.