Interleukin Antagonists
نویسندگان
چکیده
There is strong experimental and clinical support for a causal role of immune dysregulation and inflammation in atherosclerosis and heart failure. Atherosclerotic lesions are infiltrated by monocytes, macrophages, and T lymphocytes (predominantly Th1). Cytokines, including interleukin-6 (IL6) and tumor necrosis factor-α (TNF-α), are released by the infiltrating inflammatory cells and stimulate adhesion molecule expression. IL-6 can downregulate nitric oxide production and further worsen endothelial dysfunction. Progression of this inflammatory response is primarily regulated by specific patterns of cytokine expression. Interleukin 12 (IL-12) is a proinflammatory cytokine produced by many cell types, including monocytes, neutrophils, dendritic cells, macrophages, and smooth muscle cells in plaques. In addition to its primary role in initiation of cell-mediated immunity, IL-12 can indirectly affect the development of plaques by promoting Th1 cell differentiation. IL-12 induces production of reactive oxygen and nitrogen species that precipitates endothelial dysfunction. IL-12 augments the formation of atherosclerotic lesions and increases production of antioxidized low-density lipoprotein antibody in the apolipoprotein E–deficient atherosclerotic model, highlighting its active role in the initial phase of atherosclerosis. Moreover, IL-12 deficiency or functional blockade of IL-12 reduces atherogenesis and improves plaque stability in the low-density lipoprotein receptor mice. IL-12 is an endogenous inhibitor of angiogenesis and may induce autoimmune myocarditis. Ablation of interleukin 23 (IL-23) seems to improve myocardial remodeling and survival postmyocardial infarction in a rodent model. Disruption of IL-12 was recently shown to improve microvascular endothelial function in a diabetes mellitus model. Finally, a recent study found that circulating IL-12 levels were predictive of longterm prognosis after acute myocardial infarction.
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تاریخ انتشار 2017