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 Interferon (IFN)-g is well established, the role of Th2 cytokines is less clear. For example, interleukin (IL)-5 has been shown to mediate atheroprotection, while IL-4 has been reported to have no or even pro-atherogenic properties.
Therefore, we characterized the role of the Th2 cytokine 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 macrophages. This was accompanied by the induction of alternatively activated (M2) macrophages, which exhibited increased clearance of OxLDL compared to IFN-g-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 favourable plaque morphology, in part through the induction of alternatively activated macrophages.