Feb 1, 2019

Anticytokine Agents: Targeting Interleukin Signaling Pathways for the Treatment of Atherothrombosis

Circulation Research
Paul M Ridker

Abstract

The recognition that atherosclerosis is a complex chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anticytokine therapies targeting specific IL (interleukin) signaling pathways could serve as powerful adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease. Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA). The recent CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that specific targeting of IL-1β can significantly reduce cardiovascular event rates without lipid or blood pressure lowering. In CANTOS, the magnitude of benefit of this cytokine-targeted approach to atherosclerosis treatment was associated to the magnitude of reduction of the central signaling cytokine IL-6 and the downstream clinical biomarker high-sensitivity CRP (C-reactive protein). By contrast, in the recent CIRT (Cardiovascular Inflammation Reduction Trial), low-dose methotrexate neither reduced IL-1β, IL-6, or high-sensitivity CRP nor lowered cardiovascular even...Continue Reading

Mentioned in this Paper

Biological Markers
Interleukins
Diabetes Mellitus, Non-Insulin-Dependent
Monoclonal Antibodies
Tumor Necrosis Factor-alpha
Chronic Kidney Insufficiency
Interleukin-1
Chronic Inflammation
NLRP3 protein, human
TNF

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