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IL ‐33 is related to innate immune activation and sensitization to HDM in mild steroid‐free asthma
Author(s) -
Porsbjerg C.,
Baines K.,
Gibson P.,
Bergqvist A.,
Erjefält J. S.,
Sverrild A.,
Backer V.
Publication year - 2016
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12702
Subject(s) - asthma , medicine , methacholine , immunology , exhaled nitric oxide , eosinophil , sputum , inflammation , sensitization , immune system , respiratory epithelium , airway , respiratory disease , lung , pathology , spirometry , tuberculosis , surgery
Summary Background 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. Aim 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. Methods 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 (Fe NO ) 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 . Results 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 Fe NO ( 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 TLR 2 and TLR 4 ( TLR 2: r = 0.47, P = 0.04; TLR 4: 0.68, P < 0.001), as well allergy to house dust mites ( HDM s). Conclusion 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 Fe NO . These findings suggest that in mild allergic asthma, IL ‐33 may represent a link between innate immune activation and Fe NO production.