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


OBJECTIVE
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.


CONCLUSIONS
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.
Cherry
W Brett
WB
Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, Minn, USA.
Yoon
Juhan
J
Bartemes
Kathleen R
KR
Iijima
Koji
K
Kita
Hirohito
H
D015550:Cell Degranulation / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D007375:Interleukin-1; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface