title: IL-33 is related to innate immune activation and sensitization to HDM in mild steroid-free asthma.
abstract: 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.
  
  
  OBJECTIVE
  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 (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.
  
  
  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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Respiratory Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Porsbjerg
authors.affiliation: Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, NSW, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Baines
authors.affiliation: Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, NSW, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Gibson
authors.affiliation: Respiratory Medicine and Allergology and Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Bergqvist
authors.affiliation: Respiratory Medicine and Allergology and Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: J S
authors.initials: JS
authors.lastname: Erjefält
authors.affiliation: Respiratory Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Sverrild
authors.affiliation: Respiratory Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: V
authors.initials: V
authors.lastname: Backer
mesh_terms: D000818:Animals; D001249:Asthma / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D015415:Biomarkers; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D045853:Exhalation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D000067596:Interleukin-33 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012882:Skin Tests; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000067596:Interleukin-33; D051193:Toll-Like Receptors; D009569:Nitric Oxide
keywords: asthma; immunology; inflammation; innate; sputum