IL-33 reduces the development of atherosclerosis

Miller, A. M., Xu, D., Asquith, D. L., Denby, L., Li, Y., Sattar, N. , Baker, A. H., McInnes, I. B. and Liew, F. Y. (2008) IL-33 reduces the development of atherosclerosis. Journal of Experimental Medicine, 205(2), pp. 339-346. (doi:10.1084/jem.20071868) (PMID:18268038) (PMCID:PMC2271006)

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Abstract

Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which is a novel IL-1-like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE(-/-) mice on a high-fat diet. IL-33 and ST2 are present in the normal and atherosclerotic vasculature of mice and humans. Although control PBS-treated mice developed severe and inflamed atherosclerotic plaques in the aortic sinus, lesion development was profoundly reduced in IL-33-treated animals. IL-33 also markedly increased levels of IL-4, -5, and -13, but decreased levels of IFN gamma in serum and lymph node cells. IL-33 treatment also elevated levels of total serum IgA, IgE, and IgG(1), but decreased IgG(2a), which is consistent with a Th1-to-Th2 switch. IL-33 treated mice also produced significantly elevated antioxidized low-density lipoprotein (oxLDL) antibodies. Conversely, mice treated with soluble ST2, a decoy receptor that neutralizes IL-33, developed significantly larger atherosclerotic plaques in the aortic sinus of the ApoE(-/-) mice compared with control IgG-treated mice. Furthermore, coadministration of an anti-IL-5 mAb with IL-33 prevented the reduction in plaque size and reduced the amount of ox-LDL antibodies induced by IL-33. In conclusion, IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5 and ox-LDL antibodies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Xu, Dr Damo and Baker, Professor Andrew and Asquith, Dr Darren and Miller, Dr Ashley and Denby, Dr Laura and Li, Mr Yubin and Sattar, Professor Naveed
Authors: Miller, A. M., Xu, D., Asquith, D. L., Denby, L., Li, Y., Sattar, N., Baker, A. H., McInnes, I. B., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN:0022-1007
ISSN (Online):1540-9538
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
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)G0801198III -IMMUNOLOGY
483611Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY
483612Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY