The link is an original article on early online view - Not yet published

 

Interleukin-33 amplifies IgE synthesis and triggers mast cell degranulation via interleukin-4 in naïve mice†

 

M. Komai-Koma1, F. Brombacher2, P. N. Pushparaj3, B. Arendse2, C. McSharry1, J. Alexander4, R. Chaudhuri1, N. C. Thomson1, A. N. J. McKenzie5, I. McInnes1, F. Y. Liew1,3, D. Xu1,*

Article first published online: 15 JUN 2012

 

DOI: 10.1111/j.1398-9995.2012.02859.x

 

© 2012 John Wiley & Sons A/S

 

Abstract

 

Keywords:

allergen independent; IgE; IL-33; IL-4 dependent; mast cell degranulation

Abstract

Background

The regulation and function of IgE in healthy individuals and in antigen-naïve animals are not well understood. IL-33 administration increases serum IgE in mice, with unknown mechanism. We tested the hypothesis that IL-33 provides an antigen-independent stimulus for IgE production and mast cell degranulation.

 

Methods

IL-33 was administered to naïve wild-type (WT), nude and ST2−/−, IL-4−/−, IL4Rα−/− and T-or B-cell-specific IL-4Rα−/− mice. IgE and cytokines were quantified by ELISA. T- and B-lymphocyte numbers and CD40L expression were determined by flow cytometry. Anaphylaxis was measured by temperature, mast cell degranulation and histamine release.

 

Results

IL-33 enhanced IgE production in naïve WT, T-IL-4Rα−/−, but not in ST2−/−, IL-4−/−, IL-4Rα−/− or B-cell-specific IL-4Rα−/− mice, demonstrating IL-33 specificity and IL-4 dependency. Moreover, IL-4 was required for IL-33-induced B-cell proliferation and T-cell CD40L expression, which promotes IgE production. IL-33-induced IL-4 production was mainly from innate cells, including mast cells and eosinophils. IL-33 increased mast cell surface IgE, and triggered degranulation and systemic anaphylaxis in allergen-naïve WT, but not in IL-4Rα−/− mice.

 

Conclusion

IL-33 amplifies IgE synthesis and triggers anaphylaxis in naïve mice, via IL-4, independent of allergen. IL-33 may play an important role in nonatopic allergy and idiopathic anaphylaxis.

 

The most exciting thing about this article is the following aspect: -INDEPENDENT of ALLERGEN - This shows anaphylaxis - true IgE anaphylaxis - is occurring due to IL-4 - a chemical we know is produced by T cells and is expressed from mast cells, explaining how we experience anaphylaxis on anaphylaxis.

 

This will be published soon...... I will watch for the letters in response.

 

Article

il33-4ige

13/07/2012

A Newly Discovered Mechanism of Allergen specific IGE- Independent Anaphylaxis