Porsbjerg C, Baines K, Gibson P, Bergqvist A, Erjefält J S, Sverrild A, Backer V
Respiratory Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, NSW, Australia.
Clin Exp Allergy. 2016 Apr;46(4):564-74. doi: 10.1111/cea.12702.
IL-33 represents a potential link between the airway epithelium and induction of a Th2-type inflammatory response in asthma. However, the association with markers of eosinophilic airway inflammation has not previously been reported in patients with steroid-free asthma.
To describe the relationship between airway IL-33 and markers of eosinophilic airway inflammation, as well potential triggers of IL-33, in mild, steroid-free asthma.
IL-33 mRNA expression and IL-33 immunoreactivity were measured in bronchial biopsies from patients with asthma untreated with inhaled steroids and healthy individuals. Furthermore, fractional exhaled nitric oxide (FeNO) and eosinophils in sputum and BAL were measured, as well as airway hyperresponsiveness to mannitol and methacholine. Epithelial integrity was assessed by computerized image analysis on haematoxylin-stained sections, and TLR mRNA expression by PCR.
A total of 23 patients with asthma and 10 healthy individuals were examined (age: 24 years (20-40); females: 53%). The level of IL-33 mRNA expression was significantly higher in patients with asthma compared to healthy individuals (Median (IQR) 1.12 (0.78) vs. 0.86, P = 0.04). There was a positive correlation between IL-33 mRNA expression and the level of FeNO (r = 0.56, P = 0.01), whereas there was no association with airway or blood eosinophils. IL-33 expression was unrelated to loss of epithelial integrity, but correlated with an increased expression of TLR2 and TLR4 (TLR2: r = 0.47, P = 0.04; TLR4: 0.68, P < 0.001), as well allergy to house dust mites (HDMs).
In mild untreated asthma, the expression of IL-33 mRNA in bronchial mucosa is related to innate immune activation and allergic sensitization to HDM, rather than epithelial damage, and correlates with FeNO. These findings suggest that in mild allergic asthma, IL-33 may represent a link between innate immune activation and FeNO production.
白细胞介素-33（IL-33）是气道上皮与哮喘中Th2型炎症反应诱导之间的潜在联系。然而，此前尚未报道无类固醇哮喘患者中IL-33与嗜酸性气道炎症标志物之间的关联。
描述轻度无类固醇哮喘中气道IL-33与嗜酸性气道炎症标志物之间的关系，以及IL-33的潜在触发因素。
在未接受吸入类固醇治疗的哮喘患者和健康个体的支气管活检中测量IL-33 mRNA表达和IL-33免疫反应性。此外，测量呼出一氧化氮分数（FeNO）、痰液和支气管肺泡灌洗中的嗜酸性粒细胞，以及气道对甘露醇和乙酰甲胆碱的高反应性。通过苏木精染色切片的计算机图像分析评估上皮完整性，并通过聚合酶链反应测量Toll样受体（TLR）mRNA表达。
共检查了23例哮喘患者和10名健康个体（年龄：24岁（20 - 40岁）；女性：53%）。与健康个体相比，哮喘患者的IL-33 mRNA表达水平显著更高（中位数（四分位间距）1.12（0.78）对0.86，P = 0.04）。IL-33 mRNA表达与FeNO水平呈正相关（r = 0.56，P = 0.01），而与气道或血液中的嗜酸性粒细胞无关联。IL-33表达与上皮完整性丧失无关，但与TLR2和TLR4表达增加相关（TLR2：r = 0.47，P = 0.04；TLR4：0.68，P < 0.001），以及对屋尘螨（HDM）过敏。
在轻度未治疗的哮喘中，支气管黏膜中IL-33 mRNA的表达与先天免疫激活和对HDM的过敏致敏有关，而非上皮损伤，并与FeNO相关。这些发现表明，在轻度过敏性哮喘中，IL-33可能是先天免疫激活与FeNO产生之间的联系。
