Interleukin-18 as a Therapeutic Target in Acute Myocardial Infarction and Heart Failure

被引:120
作者
O'Brien, Laura C. [1 ]
Mezzaroma, Eleonora [2 ,3 ,4 ]
Van Tassell, Benjamin W. [2 ,3 ,4 ]
Marchetti, Carlo [2 ,3 ]
Carbone, Salvatore [2 ,3 ]
Abbate, Antonio [1 ,2 ,3 ]
Toldo, Stefano [2 ,3 ]
机构
[1] Virginia Commonwealth Univ, Dept Physiol & Biophys, Richmond, VA 23298 USA
[2] Virginia Commonwealth Univ, Victoria Johnson Res Labs, Richmond, VA 23298 USA
[3] Virginia Commonwealth Univ, Pauley Heart Ctr, Sch Med, Richmond, VA 23298 USA
[4] Virginia Commonwealth Univ, Sch Pharm, Richmond, VA 23298 USA
基金
美国国家卫生研究院;
关键词
GAMMA-INDUCING FACTOR; IL-18; BINDING-PROTEIN; PRESERVED EJECTION FRACTION; INTERFERON-GAMMA; NATURAL-KILLER; PROINFLAMMATORY CYTOKINES; RHEUMATOID-ARTHRITIS; SIGNALING PATHWAYS; IN-VITRO; EXPRESSION;
D O I
10.2119/molmed.2014.00034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin 18 (IL-18) is a proinflammatory cytokine in the IL-1 family that has been implicated in a number of disease states. In animal models of acute myocardial infarction (AMI), pressure overload, and LPS-induced dysfunction, IL-18 regulates cardiomyocyte hypertrophy and induces cardiac contractile dysfunction and extracellular matrix remodeling. In patients, high IL-18 levels correlate with increased risk of developing cardiovascular disease (CVD) and with a worse prognosis in patients with established CVD. Two strategies have been used to counter the effects of IL-18:IL-18 binding protein (IL-18BP), a naturally occurring protein, and a neutralizing IL-18 antibody. Recombinant human IL-18BP (r-hIL-18BP) has been investigated in animal studies and in phase I/II clinical trials for psoriasis and rheumatoid arthritis. A phase II clinical trial using a humanized monoclonal IL-18 antibody for type 2 diabetes is ongoing. Here we review the literature regarding the role of IL-18 in AMI and heart failure and the evidence and challenges of using IL-18BP and blocking IL-18 antibodies as a therapeutic strategy in patients with heart disease.
引用
收藏
页码:221 / 229
页数:9
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