Children's Research Institute, University of North Carolina at Chapel Hill, 116 Manning Dr, CB#7231, Chapel Hill, NC, 27599-7310, USA.
Division of Pediatric Allergy and Immunology, University of North Carolina, Chapel Hill, USA.
Respir Res. 2021 Dec 7;22(1):309. doi: 10.1186/s12931-021-01903-9.
Preclinical studies implicate interleukin (IL)-1β as a key mediator of asthma and have shown the efficacy of IL-1 antagonism for treatment of allergic airway inflammation; human studies in this area are lacking.
Our aim was to study the relationship of airway IL-1β to features of acute allergen-induced asthma exacerbation in humans.
Dust mite-allergic adults with mild asthma underwent inhalation challenge with Dermatophagoides farinae. Fractional exhaled nitric oxide (FeNO), induced sputum and peripheral blood samples were obtained pre- and 24 h post-challenge. Spirometry was performed before and throughout the challenge at 10-min intervals, and allergen responsiveness was defined by a 20% fall in Forced Expiratory Volume in 1 s (FEV). Sputum samples were analyzed for inflammatory cells, cytokines and chemokines. Multiple linear regression was employed to test the association between sputum IL-1β concentration and biomarkers of T helper type 2 (T2)-dominant inflammation.
Fourteen volunteers underwent inhaled allergen challenge. Allergen responsive volunteers showed a greater positive change in IL-1β in sputum following allergen challenge compared to non-responders. Higher pre-challenge sputum IL-1β was associated with greater increase in sputum IL-5 (p = 0.004), sputum eosinophils (p = 0.001) and blood IL-5 (p = 0.003) following allergen challenge. Allergen-induced sputum IL-1β production was significantly associated with sputum and blood IL-5 (p < 0.001 and p = 0.007, respectively), sputum IL-4 (p = 0.001), IL-13 (p = 0.026), eosinophils (p = 0.008) and FeNO (p = 0.03).
The positive association between production of IL-1β and biomarkers of T2 inflammation, particularly IL-5, in humans is consistent with work in animal models that demonstrates a link between IL-1β and the pathophysiology of allergic asthma. The role of IL-1β in human asthma warrants further study.
临床前研究表明白细胞介素（IL）-1β 是哮喘的关键介质，并显示出 IL-1 拮抗治疗变应性气道炎症的疗效；该领域的人体研究尚缺乏。
我们的目的是研究气道中 IL-1β 与人类变应原诱发哮喘加重的特征之间的关系。
尘螨过敏的轻度哮喘成人进行屋尘螨吸入激发。在激发前和激发后 24 小时采集呼出气一氧化氮分数（FeNO）、诱导痰和外周血样本。在挑战期间，每隔 10 分钟进行一次肺量测定，用力呼气量（FEV）下降 20%定义为变应原反应性。分析痰中炎症细胞、细胞因子和趋化因子。采用多元线性回归检验痰中 IL-1β 浓度与 Th2 型（T2）优势炎症的生物标志物之间的相关性。
14 名志愿者接受了吸入性变应原激发。与非反应者相比，变应原反应性志愿者在变应原激发后痰液中 IL-1β 的阳性变化更大。较高的激发前痰中 IL-1β 与激发后痰中 IL-5（p=0.004）、痰中嗜酸性粒细胞（p=0.001）和血中 IL-5（p=0.003）的增加显著相关。变应原诱导的痰中 IL-1β 产生与痰中和血中的 IL-5（p<0.001 和 p=0.007）、IL-4（p=0.001）、IL-13（p=0.026）、嗜酸性粒细胞（p=0.008）和 FeNO（p=0.03）显著相关。
在人类中，IL-1β 与 T2 炎症生物标志物之间的正相关，特别是 IL-5，与动物模型中 IL-1β 与变应性哮喘病理生理学之间的联系一致。IL-1β 在人类哮喘中的作用值得进一步研究。
