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J Allergy Clin Immunol. 2008 Jun;121(6):1484-90. doi: 10.1016/j.jaci.2008.04.005.

A novel IL-1 family cytokine, IL-33, potently activates human eosinophils.

Author information

1
Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minn, USA.

Abstract

BACKGROUND:

Eosinophils are likely key cells involved in the pathogenesis of asthma and allergic diseases; however, the mechanisms that regulate eosinophil dynamics and functions in mucosal tissues are incompletely understood. IL-33, which is produced by mucosal cells, is a new member of the IL-1 cytokine family. Mice injected with IL-33 display profound mucosal eosinophilia with associated pathologic changes. Although mast cells and T(H)2 cells express the IL-33 receptor, ST2, the roles of IL-33 and ST2 in eosinophil biology are unknown.

OBJECTIVES:

We investigated the effects of IL-33 on human eosinophils in vitro.

METHODS:

Eosinophils and neutrophils were isolated from blood of normal individuals and mildly atopic patients. Real-time RT-PCR and flow cytometry were used to detect ST2. Granulocyte responses to IL-33 were monitored by superoxide anion production and by degranulation; IL-5, IL-1beta, and TNF-alpha served as controls. Eosinophil survival and cytokine production were assessed by flow cytometry and ELISA, respectively.

RESULTS:

ST2 mRNA and protein were detected on eosinophils. IL-33 induced eosinophil superoxide anion production and degranulation as potently as IL-5. IL-33 also increased eosinophil survival and induced production of IL-8. Anti-ST2 inhibited eosinophil responses to IL-33. Neutrophils did not express ST2, nor did they respond to IL-33.

CONCLUSION:

IL-33 and its receptor, ST2, may play important roles in eosinophil-mediated inflammation; they may provide new therapeutic targets for controlling mucosal eosinophilic inflammation.

PMID:
18539196
PMCID:
PMC2821937
DOI:
10.1016/j.jaci.2008.04.005
[Indexed for MEDLINE]
Free PMC Article

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