Interleukin-33 exacerbates allergic bronchoconstriction in the mice via activation of mast cells

Allergy. 2015 May;70(5):514-21. doi: 10.1111/all.12590. Epub 2015 Feb 24.


Background: Interleukin-33 (IL-33) is implicated as an epithelium-derived danger signal promoting Th2-dependent responses in asthma. We hypothesized that IL-33 might also have direct effects on mast cell-driven allergic airway obstruction.

Methods: The effects of IL-33 on allergic responses in the airways of sensitized mice were assessed both in vivo and ex vivo, as well as on cultured mast cells in vitro.

Results: In vivo, the allergen-induced increase in resistance in the conducting airways was enhanced in mice pretreated with IL-33. Also, in the isolated airways, the allergen-induced contractions were increased in preparations from animals subjected to intranasal IL-33 pretreatment. These effects in vivo and ex vivo were blocked by the 5-HT2A receptor antagonist ketanserin and absent in mice without mast cells. Likewise, the IL-33-induced enhancement of the allergen response was absent in isolated airways from mice lacking the IL-33 receptor. Moreover, exposure to IL-33 increased secretion of serotonin from allergen-challenged isolated airways. In cultured mast cells, IL-33 enhanced the expression of tryptophan hydroxylase 1, serotonin synthesis, and storage, as well as the secretion of serotonin following IgE receptor cross-linking.

Conclusion: These results demonstrate that IL-33 exacerbates allergic bronchoconstriction by increasing synthesis, storage, and secretion of serotonin from the mast cell. This mechanism has implications for the development of airway obstruction in asthma.

Keywords: asthma; early allergic reaction; exacerbations; interleukin-33; serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology*
  • Bronchoconstriction / immunology*
  • Disease Models, Animal
  • Hypersensitivity / complications
  • Hypersensitivity / immunology
  • Interleukin-33 / immunology*
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Real-Time Polymerase Chain Reaction
  • Serotonin / immunology
  • Serotonin / metabolism


  • Il33 protein, mouse
  • Interleukin-33
  • Serotonin