Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction

被引：37
作者：
George, Marc Jonathan [1 ,2 ]
Jasmin, Nur Hayati [3 ]
Cummings, Valerie Taylor [3 ]
Richard-Loendt, Angela [4 ,5 ]
Launchbury, Francesca [5 ]
Woollard, Kevin [6 ]
Turner-Stokes, Tabitha [6 ]
Diaz, Ana Isabel Garcia [6 ]
Lythgoe, Mark [3 ]
Stuckey, Daniel James [3 ]
Hingorani, Aroon Dinesh [2 ,7 ]
Gilroy, Derek William [1 ]
机构：
[1] UCL, Dept Clin Pharmacol, Div Med, London, England
[2] Univ Coll London Hosp NHS Fdn Trust, Dept Clin Pharmacol, London, England
[3] UCL, Ctr Adv Biomed Imaging CABI, Div Med, London, England
[4] Univ Coll London Hosp NHS Fdn Trust, Dept Neuropathol, London, England
[5] UCL, Inst Neurol, UCL IQPath, London, England
[6] Imperial Coll London, Fac Med Immunol & Inflammat, London, England
[7] UCL, Inst Cardiovasc Sci, Ctr Translat Genom, London, England
来源：
JACC-BASIC TO TRANSLATIONAL SCIENCE | 2021年 / 6卷 / 05期
基金：
英国医学研究理事会; 英国惠康基金;
关键词：
inflammation; interleukin-6; myocardial infarction; reperfusion; IL-6; RECEPTOR; INJURY; INDUCTION; FIBROSIS; NECROSIS; HEART;
D O I：
10.1016/j.jacbts.2021.01.013
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI). IL-6 has 2 distinct signaling pathways: trans-signaling, which mediates inflammation, and classic signaling, which also has anti-inflammatoryeffects. The novel recombinant fusion protein sgp130Fc achieves exclusive trans-signaling blockade, whereas anti-IL-6 antibodies (Abs) result in panantagonism. In a rat model of reperfused MI, sgp130Fc, but not anti-IL-6-Ab, attenuated neutrophil and macrophage infiltration into the myocardium, reduced infarct size, and preserved cardiac function 28 days after MI. These data demonstrate the efficacy of exclusive IL-6 trans-signaling blockade and support further investigation of sgp130Fc as a potential novel therapy in MI. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
引用
收藏
页码：431 / 443
页数：13
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