Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma

Objective: Interleukin (IL)-33 is involved in the development of lung inflammation by inducing or amplifying Th2 type-mediated responses in various animal models of allergic asthma. The ST2 gene is a member of the IL-1 receptor family, producing a transmembrane form (ST2L) and a soluble secreted form (sST2). sST2 has been shown to block this IL-33/ST2 signaling pathway. This study aimed to investigate whether anti-IL-33 and sST2 reduced airway inflammation in a murine model of asthma. Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA), and the effect of sST2 and anti-IL-33 antibody on airway inflammation and airway hyperresponsiveness (AHR) was evaluated. Furthermore, we measured changes in various cytokines in the bronchoalveolar lavage (BAL) fluid when treated with sST2 or anti-IL-33. Results: We observed that anti-IL-33 antibody and sST2 exert a negative regulation on OVA-mediated allergic airway inflammation. Both treatments reduced total cell counts and eosinophil counts in BAL fluid and AHR to methacholine. The Th2 cytokines, such as IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after both treatments. However, there were no changes in the level of TGF-beta 1 and IL-10 after each treatment. Conclusions: These results suggest that anti-IL-33 as well as sST2 have therapeutic potential for allergic asthma through inhibition of Th2 cytokine production.