Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype

EMBO Mol Med. 2012 Oct;4(10):1072-86. doi: 10.1002/emmm.201201374.


Atherosclerotic lesions are characterized by the accumulation of oxidized LDL (OxLDL) and the infiltration of macrophages and T cells. Cytokine expression in the microenvironment of evolving lesions can profoundly contribute to plaque development. While the pro-atherogenic effect of T helper (Th) 1 cytokines, such as IFN-γ, is well established, the role of Th2 cytokines is less clear. Therefore, we characterized the role of the Th2 cytokine interleukin (IL)-13 in murine atherosclerosis. Here, we report that IL-13 administration favourably modulated the morphology of already established atherosclerotic lesions by increasing lesional collagen content and reducing vascular cell adhesion molecule-1 (VCAM-1)-dependent monocyte recruitment, resulting in decreased plaque macrophage content. This was accompanied by the induction of alternatively activated (M2) macrophages, which exhibited increased clearance of OxLDL compared to IFN-γ-activated (M1) macrophages in vitro. Importantly, deficiency of IL-13 results in accelerated atherosclerosis in LDLR(-/-) mice without affecting plasma cholesterol levels. Thus, IL-13 protects from atherosclerosis and promotes a favourable plaque morphology, in part through the induction of alternatively activated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / pathology*
  • Atherosclerosis / prevention & control*
  • Cholesterol / blood
  • Disease Models, Animal
  • Female
  • Interleukin-13 / immunology*
  • Interleukin-13 / metabolism*
  • Lipoproteins, LDL / analysis
  • Macrophage Activation*
  • Macrophages / immunology*
  • Male
  • Mice


  • Interleukin-13
  • Lipoproteins, LDL
  • Cholesterol