IL-4 regulates neutrophilic pulmonary inflammation in a mouse model of bronchial asthma

Cytokine. 2024 Mar 12;178:156563. doi: 10.1016/j.cyto.2024.156563. Online ahead of print.ABSTRACTNeutrophilic pulmonary inflammation in asthmatics substantially exacerbates the severity of the disease leading to resistance to conventional corticosteroid therapy. Many studies established the involvement of Th1- and Th17-cells and cytokines produced by them (IFNg, IL-17A, IL-17F etc.) in neutrophilic pulmonary inflammation. Recent studies revealed that IL-4 - a Th2-cytokine regulates neutrophil effector functions and migration. It was showed that IL-4 substantially reduces neutrophilic inflammation of the skin in a mouse model of cutaneous bacterial infection and blood neutrophilia in a mouse model systemic bacterial infection. However, there are no data available regarding the influence of IL-4 on non-infectious pulmonary inflammation. In the current study we investigated the effects of IL-4 in a previously developed mouse model of neutrophilic bronchial asthma. We showed that systemic administration of IL-4 significantly restricts neutrophilic inflammation of the respiratory tract probably through the suppression of Th1-/Th17-immune responses and downregulation of CXCR2. Additionally, pulmonary neutrophilic inflammation could be alleviated by IL-4-dependant polarization of N2 neutrophils and M2 macrophages, expressing anti-inflammatory TGFβ. Considering these, IL-4 might be used for reduction of exaggerated pulmonary neutrophilic inflammation and overcoming corticosteroid in...

Source: Cytokine - March 13, 2024 Category: Molecular Biology Authors: I P Shilovskiy A A Nikolskii E D Timotievich V I Kovchina L I Vishnyakova K V Yumashev K V Vinogradova M M Kaganova V E Brylina V V Tyulyubaev T E Rusak M E Dyneva O M Kurbacheva D A Kudlay M R Khaitov Source Type: research