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

W. Brett Cherry, Juhan Yoon, Kathleen R. Bartemes, Koji Iijima, Hirohito Kita

Research output: Contribution to journalArticlepeer-review

361 Scopus citations


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 TH2 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-1β, and TNF-α 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.

Original languageEnglish (US)
Pages (from-to)1484-1490
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Issue number6
StatePublished - Jun 2008


  • Eosinophils
  • IL-33
  • ST2
  • activation
  • inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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