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Identification and Predictive Value of Interleukin-6(+) Interleukin-10(+) and Interleukin-6(-) Interleukin-10(+) Cytokine Patterns in ST-Elevation Acute Myocardial Infarction
Ammirati, Enrico1,2; Cannistraci, Carlo V.3,9,15,16; Cristell, Nicole A.2; Vecchio, Viviana4; Palini, Alessio G.4; Tornvall, Per10; Paganoni, Anna M.6; Miendlarzewska, Ewa A.8,12; Sangalli, Laura M.6; Monello, Alberto; Pernow, John10; Bennermo, Marie Bjornstedt11; Marenzi, Giancarlo7; Hu, Dayi13; Uren, Neal G.14; Cianflone, Domenico2; Ravasi, Timothy15,16; Manfredi, Angelo A.5; Maseri, Attilio
关键词Acute Myocardial Infarction Bioengineering Inflammation Computational And Systems Biology Cytokines Interleukin-6 Interleukin-10
刊名CIRCULATION RESEARCH
2012-10-26
DOI10.1161/CIRCRESAHA.111.262477
111期:10页:1336-U242
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
研究领域[WOS]Cardiovascular System & Cardiology ; Hematology
关键词[WOS]CORONARY-ARTERY-DISEASE ; APPARENTLY HEALTHY-MEN ; LONG PENTRAXIN PTX3 ; C-REACTIVE PROTEIN ; HEART-DISEASE ; PROGNOSTIC-SIGNIFICANCE ; REPERFUSION INJURY ; T-CELLS ; ATHEROSCLEROSIS ; INFLAMMATION
英文摘要

Rationale: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6(+)) levels or very low-IL-6(-) levels.

Objective: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response.

Methods and Results: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6(+) STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6(-) STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6(+)S TEMI and IL-6(-)STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6(+) STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1 alpha, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta, and monokine induced by interferon-gamma. IL-10 was increased both in IL-6+ STEMI and IL-6(-) STEMI patients compared with controls. IL-6(+)IL-10(+) STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6(-)IL-10(+) STEMI patients. We combined IL-10 and monokine induced by interferon-gamma (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death.

Conclusions: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies. (Circ Res. 2012;111:1336-1348.)

语种英语
WOS记录号WOS:000310501300015
项目编号GR-2009-1608780
资助机构Italian Health Ministry ; Heart Care Foundation, Florence, Italy ; Italian Interpolytechnic School of Doctorate (SIPD) ; King Abdullah University of Science and Technology, Saudi Arabia
引用统计
被引频次:37[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56319
专题北京大学第二临床医学院_心外科
作者单位1.Heart Care Fdn, Assoc Nazl Med Cardiol Osped, I-50121 Florence, Italy
2.Politecn Milan, MOX, I-20133 Milan, Italy
3.Politecn Torino, Dept Mech, Turin, Italy
4.Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Clin Cardiovasc Biol Ctr, Milan, Italy
5.Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Proteome Biochem Unit, Milan, Italy
6.Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Flow Cytometry Resource Analyt Cytol Tech Applica, Milan, Italy
7.Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Autoimmun & Vasc Inflammat Unit, Milan, Italy
8.Univ Milan, Dept Cardiovasc Sci, Ctr Cardiol Monzino, IRCCS, Milan, Italy
9.Osped Niguarda Ca Granda, Dipartimento Cardiotoracovasc, Milan, Italy
10.Karolinska Inst, Cardiol Unit, Dept Med, Stockholm, Sweden
11.Karolinska Inst, Dept Clin Sci, Danderyd Hosp, Stockholm, Sweden
12.Univ Geneva, CMU, Dept Neurosci, Geneva, Switzerland
13.Peking Univ, Ctr Heart, Peoples Hosp, Beijing 100871, Peoples R China
14.Royal Infirm Edinburgh NHS Trust, Dept Cardiol, Edinburgh, Midlothian, Scotland
15.Univ Calif San Diego, Dept Med & Bioengn, La Jolla, CA 92093 USA
16.King Abdullah Univ Sci & Technol, Integrat Syst Biol Lab, Div Biol & Environm Sci & Engn, Div Appl Math & Comp Sci & Engn,Computat Biosci R, Thuwal 239556900, Saudi Arabia
推荐引用方式
GB/T 7714
Ammirati, Enrico,Cannistraci, Carlo V.,Cristell, Nicole A.,et al. Identification and Predictive Value of Interleukin-6(+) Interleukin-10(+) and Interleukin-6(-) Interleukin-10(+) Cytokine Patterns in ST-Elevation Acute Myocardial Infarction[J]. CIRCULATION RESEARCH,2012,111(10):1336-U242.
APA Ammirati, Enrico.,Cannistraci, Carlo V..,Cristell, Nicole A..,Vecchio, Viviana.,Palini, Alessio G..,...&Maseri, Attilio.(2012).Identification and Predictive Value of Interleukin-6(+) Interleukin-10(+) and Interleukin-6(-) Interleukin-10(+) Cytokine Patterns in ST-Elevation Acute Myocardial Infarction.CIRCULATION RESEARCH,111(10),1336-U242.
MLA Ammirati, Enrico,et al."Identification and Predictive Value of Interleukin-6(+) Interleukin-10(+) and Interleukin-6(-) Interleukin-10(+) Cytokine Patterns in ST-Elevation Acute Myocardial Infarction".CIRCULATION RESEARCH 111.10(2012):1336-U242.
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