Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma

Exp Lung Res. 2014 Mar;40(2):66-76. doi: 10.3109/01902148.2013.870261. Epub 2014 Jan 21.


Objective: Interleukin (IL)-33 is involved in the development of lung inflammation by inducing or amplifying Th2 type-mediated responses in various animal models of allergic asthma. The ST2 gene is a member of the IL-1 receptor family, producing a transmembrane form (ST2L) and a soluble secreted form (sST2). sST2 has been shown to block this IL-33/ST2 signaling pathway. This study aimed to investigate whether anti-IL-33 and sST2 reduced airway inflammation in a murine model of asthma.

Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA), and the effect of sST2 and anti-IL-33 antibody on airway inflammation and airway hyperresponsiveness (AHR) was evaluated. Furthermore, we measured changes in various cytokines in the bronchoalveolar lavage (BAL) fluid when treated with sST2 or anti-IL-33.

Results: We observed that anti-IL-33 antibody and sST2 exert a negative regulation on OVA-mediated allergic airway inflammation. Both treatments reduced total cell counts and eosinophil counts in BAL fluid and AHR to methacholine. The Th2 cytokines, such as IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after both treatments. However, there were no changes in the level of TGF- ß1 and IL-10 after each treatment.

Conclusions: These results suggest that anti-IL-33 as well as sST2 have therapeutic potential for allergic asthma through inhibition of Th2 cytokine production.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / pharmacology
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • Asthma / chemically induced*
  • Asthma / complications*
  • Asthma / metabolism
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / antagonists & inhibitors*
  • Interleukins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / adverse effects*
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Pneumonia / prevention & control*
  • Receptors, Interleukin / antagonists & inhibitors*
  • Receptors, Interleukin / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Th2 Cells / drug effects
  • Th2 Cells / metabolism
  • Th2 Cells / pathology


  • Antibodies, Anti-Idiotypic
  • Cytokines
  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Immunoglobulin G
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Receptors, Interleukin
  • Immunoglobulin E
  • Ovalbumin