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

Abstract

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.

Targeting CD64 mediates elimination of M1 but not M2 macrophages in vitro and in cutaneous inflammation in mice and patient biopsies

“…Failure to switch from a predominance of M1 to M2 causes to the perpetuation of chronic inflammation. 8 Imbalance in the M1/M2 ratio has been associated with cardiovascular diseases such as atherosclerosis, 9 metabolism-associated diseases such as diabetes and metabolic syndrome, 10 and autoimmune diseases such as multiple sclerosis, 11 systemic lupus erythematosus, 12 Crohn's disease 13 and rheumatoid arthritis. Persistence of M1 macrophages in the local inflammatory response can also prevent the resolution of inflammation in several chronic skin diseases, such as diabetes-associated skin ulcerations, 14 chronic venous ulcers, 15 and atopic dermatitis.…”

Ginsenoside Rg3 stereoisomers differentially inhibit vascular smooth muscle cell proliferation and migration in diabetic atherosclerosis

“…To our great relief, 20(S)‐Rg3 significantly improved other compositions in the plaque (increased the intraplaque content of collagen and decreased that of lipids and macrophages), and the plaque stability was actually increased. It has been reported that PPARγ agonist could block classical activation of macrophages and attenuates inflammation in diabetic atherosclerosis, thus may promote a more favourable plaque morphology 43, 44. In addition, atherosclerosis is also affected by lipid profiles and glucose metabolism 45, 46.…”

Interleukin 33 and Fibrosis: Pathogenesis Updated

“…Было по-казано, что цитокины Th1-пути, такие как IL-12, IL-18 и IFNγ, способствуют развитию атероскле-роза, тогда как Th2-цитокины IL-10, IL-5 и IL-13, напротив, имеют антиатерогенные эффекты. Первое исследование, связывающее IL-33 с ате-росклерозом, показало, что IL-33 может играть защитную роль в развитии атеросклероза посред-ством индукции IL-5, что помогает контролиро-вать баланс Th1/Th2 [5]. Miller A.M. и соавт.…”