IL-33 reduces the development of atherosclerosis

Ashley M Miller, Damo Xu, Darren L Asquith, Laura Denby, Yubin Li, Naveed Sattar, Andrew H Baker, Iain B McInnes, Foo Y Liew

Research output: Contribution to journalArticlepeer-review

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 IFNgamma 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 (ox-LDL) 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.

Original languageEnglish
Pages (from-to)339-46
Number of pages8
JournalJournal of Experimental Medicine
Volume205
Issue number2
DOIs
Publication statusPublished - 18 Feb 2008

Keywords

  • Animals
  • Antibodies, Monoclonal
  • Aorta, Thoracic
  • Apolipoproteins E
  • Atherosclerosis
  • Cells, Cultured
  • Cytokines
  • Diet, Atherogenic
  • Endothelial Cells
  • Humans
  • Immunoglobulins
  • Interleukin-33
  • Interleukin-5
  • Interleukins
  • Lipoproteins, LDL
  • Macrophages
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Smooth Muscle
  • RNA, Messenger
  • Receptors, Interleukin
  • T-Lymphocytes

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