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
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
收藏
页码：221 / 229
页数：9
相关论文
共 101 条
[1]   Effects of Interleukin-1 Blockade With Anakinra on Adverse Cardiac "Remodeling and Heart Failure After Acute Myocardial Infarction [from the Virginia Commonwealth. University-Anakinra Remodeling Trial (2) (VCU-ART2) Pilot Study] [J].
Abbate, Antonio ;
Van Tassel, Benjamin Wallace ;
Biondi-Zoccai, Giuseppe ;
Kontos, Michael Christopher ;
Grizzard, John Dallas ;
Spillman, Debra Whittaker ;
Oddi, Claudia ;
Roberts, Charlotte Susan ;
Melchior, Ryan David ;
Mueller, George Herman ;
Abouzaki, Nayef Antar ;
Rengel, Lenore Rosemary ;
Varma, Amit ;
Gambill, Michael Lucas ;
Falcao, Raquel Appa ;
Voelkel, Norbert Felix ;
Dinarello, Charles Anthony ;
Vetrovec, George Wayne .
AMERICAN JOURNAL OF CARDIOLOGY, 2013, 111 (10) :1394-1400
[2]   Interleukin-1 Blockade With Anakinra to Prevent Adverse Cardiac Remodeling After Acute Myocardial Infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot Study) [J].
Abbate, Antonio ;
Kontos, Michael C. ;
Grizzard, John D. ;
Biondi-Zoccai, Giuseppe G. L. ;
Van Tassell, Benjamin W. ;
Robati, Roshanak ;
Roach, Lenore M. ;
Arena, Ross A. ;
Roberts, Charlotte S. ;
Varma, Amit ;
Gelwix, Christopher C. ;
Salloum, Fadi N. ;
Hastillo, Andrea ;
Dinarello, Charles A. ;
Vetrovec, George W. .
AMERICAN JOURNAL OF CARDIOLOGY, 2010, 105 (10) :1371-1377
[3]   Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].
Adachi, O ;
Kawai, T ;
Takeda, K ;
Matsumoto, M ;
Tsutsui, H ;
Sakagami, M ;
Nakanishi, K ;
Akira, S .
IMMUNITY, 1998, 9 (01) :143-150
[4]  
Ahn HJ, 1997, J IMMUNOL, V159, P2125
[5]   Involvement of caspase-1 and caspase-3 in the production and processing of mature human interleukin 18 in monocytic THP.1 cells [J].
Akita, K ;
Ohtsuki, T ;
Nukada, Y ;
Tanimoto, T ;
Namba, M ;
Okura, T ;
TakakuraYamamoto, R ;
Torigoe, K ;
Gu, Y ;
Su, MSS ;
Fujii, M ;
SatohItoh, M ;
Yamamoto, K ;
Kohno, K ;
Ikeda, M ;
Kurimoto, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (42) :26595-26603
[6]  
[Anonymous], IL 1 BLOCK AC MYOC I
[7]  
Artlett Carol M, 2012, Open Rheumatol J, V6, P80, DOI 10.2174/1874312901206010080
[8]   A newly defined interleukin-1? [J].
Bazan, JF ;
Timans, JC ;
Kastelein, RA .
NATURE, 1996, 379 (6566) :591-591
[9]   M-CSF induces the expression of a membrane-bound form of IL-18 in a subset of human monocytes differentiating in vitro toward macrophages [J].
Bellora, Francesca ;
Castriconi, Roberta ;
Doni, Andrea ;
Cantoni, Claudia ;
Moretta, Lorenzo ;
Mantovani, Alberto ;
Moretta, Alessandro ;
Bottino, Cristina .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2012, 42 (06) :1618-1626
[10]   Interleukin-18 and the risk of coronary heart disease in European men -: The Prospective Epidemiological Study of Myocardial Infarction (PRIME) [J].
Blankenberg, S ;
Luc, G ;
Ducimetière, P ;
Arveiler, D ;
Ferrières, J ;
Amouyel, P ;
Evans, A ;
Cambien, F ;
Tiret, L .
CIRCULATION, 2003, 108 (20) :2453-2459
12345678910