IL-33 is a mediator rather than a trigger of the acute allergic response in humans

Fux, Michaela; Pecaric-Petkovic, T.; Odermatt, A.; Hausmann, Oliver; Lorentz, A.; Bischoff, S. C.; Virchow, J. C.; Dahinden, Clemens A. (2014). IL-33 is a mediator rather than a trigger of the acute allergic response in humans. Allergy, 69(2), pp. 216-222. Wiley-Blackwell 10.1111/all.12309

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BACKGROUND IL-33 enhances FcεRI-induced mediator release in human basophils without inducing degranulation itself. In contrast, studies in mice suggested that in the presence of high IgE 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 IgE levels by regulating exocytosis independent of FcεRI cross-linking. Furthermore, we investigated whether IL-33 is released upon allergen provocation in vivo. METHODS In subjects with high serum IgE levels, we measured IL-33-induced histamine/LTC4 in vitro, CD63 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 (BALFs) after allergen challenge. RESULTS IL-33 itself does not trigger basophil degranulation in vitro and ex vivo, even in subjects with high serum IgE levels, and negative SPTs 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 BALFs 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 IgE levels. However, the rapid release of IL-33 upon allergen provocation in vivo supports its role as a mediator of immediate allergic responses.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Fux, Michaela; Pecaric, Tatjana; Hausmann, Oliver and Dahinden, Clemens A.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0105-4538

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Stefan Kuchen

Date Deposited:

17 Jul 2014 16:45

Last Modified:

06 Nov 2015 09:18

Publisher DOI:

10.1111/all.12309

PubMed ID:

24205920

Uncontrolled Keywords:

IL-33, IgE, asthma, basophil/mast cell degranulation, bronchoalveolar lavage fluids

BORIS DOI:

10.7892/boris.42903

URI:

https://boris.unibe.ch/id/eprint/42903

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