IL-1R1 but not IL-18BP contributes to the beneficial effects of IL-37 on allergic asthma
23.Februar 2017 (online)
An impaired production of the anti-inflammatory cytokine IL-37 in allergic asthmatics suggests a role for IL-37 in asthma pathogenesis. We have previously shown that the local application of IL-37 ameliorates experimental asthma via a mechanism that requires IL-18 receptor (R) α and single Ig IL-1-related receptor (SIGIRR). This study is aimed to elucidate the role of IL-18BP and IL-1R1 in IL-37 signaling.
Experimental asthma was induced in IL-18BP-deficient and IL-1R1-deficient mice. IL-37 was applied intratrachealy during allergen challenge. Infiltration of eosinophils, cytokine production, mucus production and airway hyperresponsiveness (AHR) were assessed and compared to a healthy and an asthmatic control group.
IL-37 treatment of IL-18PB-deficient mice reduced the level of pro-inflammatory cytokines, eosinophils infiltration, mucus-hyper-production and AHR, which was comparable to the effects seen in wildtype animals. In contrast, IL-37 treatment of IL-1R1-deficient mice reduced AHR, but had no influence in the airway inflammation or the mucus production.
In contrast to in-vitro results that suggested a synergistic function of IL-37 and IL-18BP, our results demonstrate that the effects of IL-37 on experimental asthma are not markedly affected by IL-18BP. Since IL-37 was unable to reduce airway inflammation in IL-1R1-deficient mice, our study indicates that IL-37 might function via a SIGIRR-mediated blockade of the pro-inflammatory IL-1 signaling.