Role of IL-33/ST2 axis in systemic inflammation of allergic airway disease

Introduction: T helper 2 (Th2) lymphocytes play an important role in chronic inflammatory process of allergic disease. IL-33 targeting ST2 receptor selectively expressed on Th2 cells surface, regulates the production of cytokines as IL-17A and IL-31. Aim: To evaluate the role of IL-33/ST2 axis in the IL-31 and IL-17 production during systemic inflammation of patients with allergic rhinitis (AR) and concomitant allergic asthma and rhinitis (AAR) compared to healthy control subjects (HC). Methods: 20 HC, 14 AR and 17 AAR subjects were recruited and blood samples collected. IL-31, IL-33, and IL-17A plasma concentrations were measured by commercial ELISA. IL-17A and IL-31 production, and ST2 receptor expression were evaluated by flow-cytometric analysis in PBMC from HC, AR, AAR (n=6 for each group). Finally, the in vitro activity of Beclomethasone Dipropionate (BDP) (10-8M to 10-7M) was evaluated on IL-17A and IL-31 production, together with ST2 receptor expression in PBMC from AAR (n=6). Results: IL-17A, IL-31 and IL-33 plasma levels were significantly higher in patients with AR and AAR than in HC. IL-31 and IL-17A intracellular levels significantly increased in PBMC from AR and AAR compared to HC while ST2 receptor expression was significantly lower. Finally, IL-17A and IL-31 intracellular levels were decreased by BDP treatment, while ST2 receptor expression increased in cultured PBMCs from AAR. Conclusions: IL-33/ST2 axis activation is a biomarker of Th2/IL-31 and Th17 immune response in the allergic airway disease. Finally, a potential therapeutic approach by BDP might be useful treatment to control Th2/IL-31 and Th17 immune response, in patients with concomitant allergic asthma and rhinitis.