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

被引：121

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

来源：

MOLECULAR MEDICINE | 2014年 / 20卷

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

页码：221 / 229

页数：9

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