Interleukin-36 receptor antagonist alleviates airway inflammation in asthma via inhibiting the activation of Interleukin-36 pathway

Abstract

Backgrounds: Asthma is characterized as an inflammatory disorder in the respiratory system with increasing tendency. Most of the asthma patients suffered from the disease since childhood. Thus, developing novel therapeutic targets of pediatric asthma is necessary. Here, we conducted the present study to investigate the effects of IL-36RN (Interleukin-36 receptor antagonist), a newly identified anti-inflammatory factor, on asthma.

Methods: Sixty asthmatic children (30 moderate and 30 mild) were recruited. The levels of IL-36RN in peripheral blood mononuclear cells (PBMCs), serum and induced sputum (IS) samples from asthma patients and healthy controls (HCs) were measured by qPCR and ELISA. The anti-inflammatory effects of IL-36RN were determined in vitro and potential therapeutic effect on asthma was evaluated in the mouse model of asthma.

Results: The mRNA and protein levels of IL-36RN were significant down-regulated in asthmatics than HCs. The IL-36RN significantly suppressed the expression of pro-inflammatory factors in PBMCs and sputum cells from asthma patients in vitro. And delivering IL-36RN into the mouse model of asthma showed disease alleviation. Pathway analysis showed that the IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway.

Conclusion: Our data here indicated that IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway.

Keywords: Asthma; IL-36; IL-36RN; Interleukin-36 receptor antagonist.