Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
J Asthma. 2023 Jul;60(7):1455-1465. doi: 10.1080/02770903.2022.2155186. Epub 2022 Dec 13.
Allergic asthma is often associated with eosinophilic inflammation, which is related to the T-helper cell type 2 (Th2) cytokines and responsive to corticosteroids. However, there are also phenotypes of non-Th2-mediated asthma, which have poor responsivity to corticosteroids. The leading phenotype of non-Th2-mediated asthma is neutrophilic asthma, which is considered difficult to treat. Recently, IL-22 has been found to be involved in neutrophilic inflammation in asthma. However, studies on the role of IL-22 in asthma are still controversial as IL-22 has both pro-inflammatory and anti-inflammatory roles in asthma. This study examined whether the IL-22 level increased in acute neutrophilic asthma in the mouse model. Herein, we aimed to demonstrate increased IL-22 levels in neutrophilic asthma and elucidate the pathways leading to elevated neutrophil counts. Six-week old female BALB/c mice were sensitized and challenged with PBS, ovalbumin (OVA) or OVA + lipopolysaccharide (LPS). The mice were then assigned to one of the following five groups: (1) control (PBS/ PBS), (2) OVA/PBS, (3) OVA/OVA, (4) OVA+LPS/PBS, (5) OVA+LPS/OVA+LPS. The levels of Th2 cytokines, IL-17, and IL-22 were assessed, with investigation of the neutrophil chemokines. This study showed that in the acute neutrophilic asthma, the levels of IL-17 and IL-22 were significantly higher than those in the OVA/OVA group, which represents acute eosinophilic asthma. Moreover, the level of CCL20 increased in the neutrophilic asthma group. Thus, this study suggests that in the acute neutrophilic asthma mouse model, IL-17 and IL-22 may increase with CCL20, resulting in neutrophilic inflammation.
变应性哮喘常伴有嗜酸性粒细胞炎症，这与辅助性 T 细胞 2（Th2）细胞因子有关，并对皮质类固醇有反应。然而，也存在非 Th2 介导的哮喘表型，对皮质类固醇反应不佳。非 Th2 介导的哮喘的主要表型是中性粒细胞性哮喘，被认为难以治疗。最近，发现白细胞介素 22（IL-22）参与哮喘中的中性粒细胞炎症。然而，IL-22 在哮喘中的作用仍存在争议，因为 IL-22 在哮喘中具有促炎和抗炎作用。本研究旨在探讨 IL-22 水平是否在小鼠模型的急性中性粒细胞性哮喘中升高。在此，我们旨在证明中性粒细胞性哮喘中 IL-22 水平升高，并阐明导致中性粒细胞计数升高的途径。将 6 周龄雌性 BALB/c 小鼠致敏并用磷酸盐缓冲液（PBS）、卵清蛋白（OVA）或 OVA+脂多糖（LPS）进行攻毒。然后将小鼠分为以下五组之一：（1）对照（PBS/PBS）、（2）OVA/PBS、（3）OVA/OVA、（4）OVA+LPS/PBS、（5）OVA+LPS/OVA+LPS。评估 Th2 细胞因子、IL-17 和 IL-22 的水平，并研究中性粒细胞趋化因子。本研究表明，在急性中性粒细胞性哮喘中，IL-17 和 IL-22 的水平明显高于代表急性嗜酸性粒细胞性哮喘的 OVA/OVA 组。此外，中性粒细胞性哮喘组中 CCL20 的水平增加。因此，本研究表明，在急性中性粒细胞性哮喘小鼠模型中，IL-17 和 IL-22 可能与 CCL20 一起增加，导致中性粒细胞炎症。
