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IL ‐33 is a mediator rather than a trigger of the acute allergic response in humans
Author(s) -
Fux M.,
PecaricPetkovic T.,
Odermatt A.,
Hausmann O. V.,
Lorentz A.,
Bischoff S. C.,
Virchow J. C.,
Dahinden C. A.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12309
Subject(s) - immunology , degranulation , immunoglobulin e , histamine , basophil , allergy , allergen , tryptase , medicine , ex vivo , provocation test , in vivo , eosinophil , anaphylaxis , allergic response , asthma , mast cell , biology , antibody , receptor , pathology , microbiology and biotechnology , alternative medicine
Background IL ‐33 enhances F cε RI ‐induced mediator release in human basophils without inducing degranulation itself. In contrast, studies in mice suggested that in the presence of high I g E levels, IL ‐33 triggers degranulation and anaphylaxis of similar severity as specific allergen. Consistent with this view, sera of atopic patients contain elevated levels of IL ‐33 after anaphylaxis. In this study, we determined whether IL ‐33 is potentially anaphylactogenic in humans with high I g E levels by regulating exocytosis independent of Fcε RI cross‐linking. Furthermore, we investigated whether IL ‐33 is released upon allergen provocation in vivo . Methods In subjects with high serum I g E levels, we measured IL ‐33‐induced histamine/ LTC 4 in vitro , CD 63 translocation ex vivo , and responsiveness of mast cells in vivo by skin prick test ( SPT ). In asthma patients, release of IL ‐33 and its correlation with early (tryptase)‐ and late‐phase markers ( IL ‐13 levels, eosinophil numbers) of the allergic response were assessed in bronchoalveolar lavage fluids ( BALF s) after allergen challenge. Results IL ‐33 itself does not trigger basophil degranulation in vitro and ex vivo , even in subjects with high serum I g E levels, and negative SPT s demonstrate that skin mast cells do not degranulate in response to IL ‐33. However, in response to allergen challenge, IL ‐33 is rapidly released into BALF s at levels that do not correlate with other immediate‐ and late‐phase parameters. Conclusion IL ‐33 is unlikely an independent trigger of anaphylaxis even in subjects with high I g E levels. However, the rapid release of IL ‐33 upon allergen provocation in vivo supports its role as a mediator of immediate allergic responses.