Pushparaj, P. N., Tay, H. K., H'Ng, S. C., Pitman, N., Xu, D., McKenzie, A., Liew, F. Y. and Melendez, A. J. (2009) The cytokine interleukin-33 mediates anaphylactic shock. Proceedings of the National Academy of Sciences of the United States of America, 106(24), pp. 9773-9778. (doi: 10.1073/pnas.0901206106)
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Publisher's URL: http://dx.doi.org/10.1073/pnas.0901206106
Abstract
Anaphylactic shock is characterized by elevated immunoglobulin-E (IgE) antibodies that signal via the high affinity Fcε receptor (FcεRI) to release inflammatory mediators. Here we report that the novel cytokine interleukin-33 (IL-33) potently induces anaphylactic shock in mice and is associated with the symptom in humans. IL-33 is a new member of the IL-1 family and the ligand for the orphan receptor ST2. In humans, the levels of IL-33 are substantially elevated in the blood of atopic patients during anaphylactic shock, and in inflamed skin tissue of atopic dermatitis patients. In murine experimental atopic models, IL-33 induced antigen-independent passive cutaneous and systemic anaphylaxis, in a T cell–independent, mast cell–dependent manner. In vitro, IL-33 directly induced degranulation, strong eicosanoid and cytokine production in IgE-sensitized mast cells. The molecular mechanisms triggering these responses include the activation of phospholipase D1 and sphingosine kinase1 to mediate calcium mobilization, Nuclear factor–κB activation, cytokine and eicosanoid secretion, and degranulation. This report therefore reveals a hitherto unrecognized pathophysiological role of IL-33 and suggests that IL-33 may be a potential therapeutic target for anaphylaxis, a disease of considerable unmet medical need.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Liew, Prof Foo and Xu, Dr Damo and Tay, Dr Hwee Kee and Pushparaj, Dr Peter |
| Authors: | Pushparaj, P. N., Tay, H. K., H'Ng, S. C., Pitman, N., Xu, D., McKenzie, A., Liew, F. Y., and Melendez, A. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Related URLs: |
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