Hasegawa Takehiro, Uga Hitoshi, Mori Akio, Kurata Hirokazu
Sysmex Corporation, Kobe, Japan, Division of System Biology of Disease, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
Sysmex Corporation, Kobe, Japan.
Eur Cytokine Netw. 2017 Mar 1;28(1):8-18. doi: 10.1684/ecn.2017.0390.
Asthma is a syndrome of chronic bronchial inflammation and airway remodelling. Initially, asthma has been categorized into atopic and nonatopic types, based on antigen-specific IgE levels. Moreover, recently, asthma has been classified into different endotypes based on its pathophysiology, leading to the selection of the most optimal and effective therapies. Although T helper cell type 2 (Th2) cytokines were proven to play critical roles in atopic asthma, IL-17A has been reported to be involved in severe refractory asthma. In this study, we measured the levels of 24 cytokines/chemokines in the sera of healthy controls (HCs) (n = 34) and patients with asthma (n = 77), that were compared among patient groups with different disease activities and characteristics. The serum levels of nine cytokines were significantly higher in patients with asthma than in HCs, and the levels of IL-17A and SCF were significantly different between uncontrolled and well-controlled patient groups (p = 0.003). The IL-17A levels were significantly correlated with those of IL-4, IL-25, IL-10, and IFN-γ in patients with uncontrolled asthma, and the patients with the highest levels of all the above cytokines were refractory to high-dose of inhaled corticosteroid therapy and have a history of acute exacerbation within 1 year, requiring systemic steroid therapy. This study examines the profiles of upregulation and downregulation of various cytokines and chemokines in relation to asthmatic control status. IL-17A was significantly upregulated in patients with the uncontrolled and refractory status. Therefore, IL-17A may play important roles in asthmatic exacerbation, and its high level, in combination with upregulated Th2 and other cytokines, may indicate the refractory endotype of asthma.
哮喘是一种慢性支气管炎症和气道重塑综合征。最初，哮喘根据抗原特异性IgE水平被分为特应性和非特应性类型。此外，近来哮喘根据其病理生理学被分为不同的内型，从而有助于选择最优化和有效的治疗方法。尽管已证实2型辅助性T细胞（Th2）细胞因子在特应性哮喘中起关键作用，但有报道称白细胞介素-17A（IL-17A）与重度难治性哮喘有关。在本研究中，我们检测了健康对照者（HCs，n = 34）和哮喘患者（n = 77）血清中24种细胞因子/趋化因子的水平，并在具有不同疾病活动度和特征的患者组之间进行比较。哮喘患者血清中9种细胞因子水平显著高于HCs，且IL-17A和干细胞因子（SCF）水平在未控制和控制良好的患者组之间存在显著差异（p = 0.003）。在未控制的哮喘患者中，IL-17A水平与IL-4、IL-25、IL-10和干扰素-γ（IFN-γ）水平显著相关，且上述所有细胞因子水平最高的患者对高剂量吸入性糖皮质激素治疗无效，并有1年内急性加重病史，需要全身用糖皮质激素治疗。本研究探讨了各种细胞因子和趋化因子上调和下调与哮喘控制状态的关系。IL-17A在未控制和难治性状态的患者中显著上调。因此，IL-17A可能在哮喘加重中起重要作用，其高水平与Th2及其他细胞因子上调相结合，可能提示哮喘的难治性内型。
