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

Fux, Michaela; Pecaric‐Petkovic, Tatjana; Odermatt, Andrea; Hausmann, Oliver; Lorentz, Axel; Bischoff, Stephan C.; Virchow, J. Christian; Dahinden, Clemens A.

doi:10.1111/all.12309

Cited by 60 publications

(51 citation statements)

References 34 publications

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“…Elevated sST2 levels in allergic asthmatics suggest localized production of sST2 within the airways that may act as an inhibitor of IL-33-induced inflammation. This has been demonstrated in cases of sepsis and asthma exacerbation [36, 39, 40]. …”

Section: Discussionmentioning

confidence: 98%

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

Mitchell

Salter

Oliveria

et al. 2018

Int Arch Allergy Immunol

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Background: Previous murine models have demonstrated interleukin (IL)-33 to be an important mediator of type-2 inflammation and to promote airway hyperresponsiveness in allergic asthma. A number of inflammatory cells produce IL-33 and eosinophils express ST2 mRNA. The relationship between IL-33 and eosinophils in allergic asthma, however, remains unclear. Objective: The aim of this work was to evaluate in vitro the effect of allergen inhalation on IL-33 levels and expression of its receptor (ST2L) on eosinophils in allergic asthmatics, and the effect of IL-33 stimulation on eosinophil activity. Methods: Plasma and sputum IL-33, soluble ST2 (sST2) levels, and ST2L expression on eosinophils were measured in 10 healthy controls and 10 allergic asthmatics. Asthmatics underwent allergen and diluent inhalation challenges. Blood and sputum samples were collected to measure IL-33, sST2, and ST2L eosinophil expression before and 24 h after allergen inhalation. Purified blood eosinophils from allergic asthmatics were incubated overnight with IL-33 to assess ST2 and intracellular IL-5 expression. Results: Baseline levels of IL-33 in sputum and sST2 in plasma and sputum were similar in allergic asthmatics compared to healthy controls. In addition, there was no difference in blood or sputum eosinophil ST2L expression in healthy controls versus allergic asthmatics. Eosinophil ST2L expression was significantly increased 24 h postallergen inhalation in allergic asthmatics. In vitro stimulation of human eosinophils with IL-33 and LPS significantly increased eosinophil ST2L expression and IL-33 stimulation increased intracellular IL-5 expression, which was attenuated by treatment with sST2 and ST2 blockade. Conclusion and Clinical Relevance: In mild asthmatics, there was a significant upregulation of ST2 surface expression on eosinophils from blood and sputum following allergen inhalation challenge. In vitro, IL-33 stimulation of eosinophils increases both ST2 membrane expression and IL-5 production. These results support a role for IL-33 in causing allergen-induced eosinophilia. Blockade of IL-33 and ST2 signaling may present a novel therapeutic avenue for asthma treatment.

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Section: Discussionmentioning

confidence: 98%

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

Mitchell

Salter

Oliveria

et al. 2018

Int Arch Allergy Immunol

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“…Once stimulated, MCs secrete numerous vasoactive and proinflammatory mediators, leading to multiple symptoms (Theoharides et al, 2012a). MC activation can be enhanced by IL-33 (Fux et al, 2014), which synergizes with SP to induce VEGF release (Theoharides et al, 2010), acting as a "sensor of cell injury" (Enoksson et al, 2011;Theoharides et al, 2015a).…”

Section: Pathogenesismentioning

confidence: 99%

Fibromyalgia Syndrome in Need of Effective Treatments

Theoharides

Tsilioni

Arbetman

et al. 2015

J Pharmacol Exp Ther

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Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.

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“…The effect of IL-33 on MCs was reviewed recently (Sabatino et al, 2012). ST2 is expressed on MCs, for which it acts as a chemoattractant and augments the effect of other triggers (Fux et al, 2014). MCs respond to cell injury through IL-33 (Lunderius-Andersson et al, 2012) and have therefore been considered "sensors of cell injury" (Enoksson et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Targeting IL-33 in Autoimmunity and Inflammation

Theoharides

Petra

Taracanova

et al. 2015

J Pharmacol Exp Ther

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

Abstract: 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.

Cited by 60 publications

References 34 publications

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics

Fibromyalgia Syndrome in Need of Effective Treatments

Targeting IL-33 in Autoimmunity and Inflammation

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