IL-33 promotes airway remodeling and is a marker of asthma disease severity

J Asthma. 2014 Oct;51(8):863-9. doi: 10.3109/02770903.2014.921196. Epub 2014 Jun 5.

Abstract

Objective: To investigate the function of interleukin-33 (IL-33) in the asthmatic airway remodeling and the relationship between IL-33 and asthma severity.

Methods: IL-33 levels, sputum eosinophils percentage (EOS%), pulmonary function and total immunoglobulin (IgE) were measured for 45 patients with asthma and 40 non-allergic controls. Asthma severity was assessed. The expressions of IL-33 and reticular basement membrane (RBM) on bronchial biopsy specimens from eight asthma patients and eight non-allergic controls were observed after hematoxylin-eosin staining (HE) and immunohistochemical staining. In vitro experiments, real-time polymerase chain reactions and western blotting analysis were used to identify the specific effects of IL-33 administration.

Results: Serum IL-33 levels in patients with asthma were higher than those in non-allergic controls. Moreover, in asthmatic patients, serum IL-33 levels were negatively correlated to forced expiratory volume in one second (FEV1, % predicted), and positively correlated to asthma severity. Increased expression of IL-33 and RBM thickening were observed on bronchial biopsy specimens obtained from patients with asthma. Serum IL-33 levels were positively correlated to basement membrane thickness. The production of fibronectin1 and type I collagen in human lung fibroblasts (HLF-1) increased at 24 h after IL-33 treatment in vitro. Pre-treatment with anti-ST2 antibody or fluticasone propionate (FP) suppressed the production of fibronectin1 and types I collagen induced by IL-33.

Conclusions: IL-33 is a marker of asthma severity, and may contribute to airway remodeling in asthma by acting on human lung fibroblasts.

Keywords: Airway remodeling; HLF-1; IL-33; ST2; asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Airway Remodeling / physiology*
  • Asthma / blood*
  • Asthma / physiopathology*
  • Biomarkers / blood
  • Female
  • Humans
  • Interleukin-33
  • Interleukins / blood*
  • Interleukins / physiology*
  • Male
  • Severity of Illness Index

Substances

  • Biomarkers
  • IL33 protein, human
  • Interleukin-33
  • Interleukins