The cytokine interleukin-33 mediates anaphylactic shock

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, Professor 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 > Institute of Infection Immunity and Inflammation
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
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
241511Characterisation of genes differentially expressed on subsets of T lymphocytesFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine
380241Toll-like receptors on T cellsFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198Infection Immunity and Inflammation Medicine
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794Institute of Infection Immunity and Inflammation