Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6-interleukin-10+ cytokine patterns in st-elevation acute myocardial infarction

Handle URI:
http://hdl.handle.net/10754/562282
Title:
Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6-interleukin-10+ cytokine patterns in st-elevation acute myocardial infarction
Authors:
Ammirati, Enrico; Cannistraci, Carlo; Cristell, Nicole A.; Vecchio, Viviana; Palini, Alessio G.; Tornvall, Per; Paganoni, Anna Maria; Miendlarzewska, Ewa A.; Sangalli, Laura Maria; Monello, Alberto; Pernow, John; Björnstedt Bennermo, Marie; Marenzi, Giancarlo Carlo; Hu, Dayi; Uren, Neal G.; Cianflone, Domenico; Ravasi, Timothy ( 0000-0002-9950-465X ) ; Manfredi, Angelo A.; Maseri, Attilio
Abstract:
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 STEMI 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-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6 STEMI and IL-6 STEMI patients compared with controls. IL-6IL-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-6IL-10 STEMI patients. We combined IL-10 and monokine induced by interferon-γ (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. © 2012 American Heart Association, Inc.
KAUST Department:
Applied Mathematics and Computational Science Program; Biological and Environmental Sciences and Engineering (BESE) Division; Integrative Systems Biology Lab; Bioscience Program; Computational Bioscience Research Center (CBRC)
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Journal:
Circulation Research
Issue Date:
29-Aug-2012
DOI:
10.1161/CIRCRESAHA.111.262477
PubMed ID:
22931953
Type:
Article
ISSN:
00097330
Sponsors:
E. Ammirati received financial support from Giovane Ricercatore 2009 Grant from the Italian Health Ministry (project code GR-2009-1608780) and from the Heart Care Foundation, Florence, Italy. C. V. Cannistraci was supported by the Italian Interpolytechnic School of Doctorate (SIPD). T. Ravasi and C. V. Cannistraci received financial support from King Abdullah University of Science and Technology, Saudi Arabia.
Appears in Collections:
Articles; Bioscience Program; Applied Mathematics and Computational Science Program; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorAmmirati, Enricoen
dc.contributor.authorCannistraci, Carloen
dc.contributor.authorCristell, Nicole A.en
dc.contributor.authorVecchio, Vivianaen
dc.contributor.authorPalini, Alessio G.en
dc.contributor.authorTornvall, Peren
dc.contributor.authorPaganoni, Anna Mariaen
dc.contributor.authorMiendlarzewska, Ewa A.en
dc.contributor.authorSangalli, Laura Mariaen
dc.contributor.authorMonello, Albertoen
dc.contributor.authorPernow, Johnen
dc.contributor.authorBjörnstedt Bennermo, Marieen
dc.contributor.authorMarenzi, Giancarlo Carloen
dc.contributor.authorHu, Dayien
dc.contributor.authorUren, Neal G.en
dc.contributor.authorCianflone, Domenicoen
dc.contributor.authorRavasi, Timothyen
dc.contributor.authorManfredi, Angelo A.en
dc.contributor.authorMaseri, Attilioen
dc.date.accessioned2015-08-03T09:59:18Zen
dc.date.available2015-08-03T09:59:18Zen
dc.date.issued2012-08-29en
dc.identifier.issn00097330en
dc.identifier.pmid22931953en
dc.identifier.doi10.1161/CIRCRESAHA.111.262477en
dc.identifier.urihttp://hdl.handle.net/10754/562282en
dc.description.abstractRATIONALE: 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 STEMI 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-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6 STEMI and IL-6 STEMI patients compared with controls. IL-6IL-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-6IL-10 STEMI patients. We combined IL-10 and monokine induced by interferon-γ (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. © 2012 American Heart Association, Inc.en
dc.description.sponsorshipE. Ammirati received financial support from Giovane Ricercatore 2009 Grant from the Italian Health Ministry (project code GR-2009-1608780) and from the Heart Care Foundation, Florence, Italy. C. V. Cannistraci was supported by the Italian Interpolytechnic School of Doctorate (SIPD). T. Ravasi and C. V. Cannistraci received financial support from King Abdullah University of Science and Technology, Saudi Arabia.en
dc.publisherOvid Technologies (Wolters Kluwer Health)en
dc.subjectacute myocardial infarctionen
dc.subjectbioengineeringen
dc.subjectcomputational and systems biologyen
dc.subjectcytokinesen
dc.subjectinflammationen
dc.subjectinterleukin-10en
dc.subjectinterleukin-6en
dc.titleIdentification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6-interleukin-10+ cytokine patterns in st-elevation acute myocardial infarctionen
dc.typeArticleen
dc.contributor.departmentApplied Mathematics and Computational Science Programen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentIntegrative Systems Biology Laben
dc.contributor.departmentBioscience Programen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalCirculation Researchen
dc.contributor.institutionHeart Care Fdn, Assoc Nazl Med Cardiol Osped, I-50121 Florence, Italyen
dc.contributor.institutionUniv Vita Salute San Raffaele, San Raffaele Sci Inst, Clin Cardiovasc Biol Ctr, Milan, Italyen
dc.contributor.institutionUniv Vita Salute San Raffaele, San Raffaele Sci Inst, Proteome Biochem Unit, Milan, Italyen
dc.contributor.institutionUniv Vita Salute San Raffaele, San Raffaele Sci Inst, Flow Cytometry Resource Analyt Cytol Tech Applica, Milan, Italyen
dc.contributor.institutionUniv Vita Salute San Raffaele, San Raffaele Sci Inst, Autoimmun & Vasc Inflammat Unit, Milan, Italyen
dc.contributor.institutionPolitecn Milan, MOX, I-20133 Milan, Italyen
dc.contributor.institutionUniv Milan, Dept Cardiovasc Sci, Ctr Cardiol Monzino, IRCCS, Milan, Italyen
dc.contributor.institutionOsped Niguarda Ca Granda, Dipartimento Cardiotoracovasc, Milan, Italyen
dc.contributor.institutionPolitecn Torino, Dept Mech, Turin, Italyen
dc.contributor.institutionKarolinska Inst, Cardiol Unit, Dept Med, Stockholm, Swedenen
dc.contributor.institutionKarolinska Inst, Dept Clin Sci, Danderyd Hosp, Stockholm, Swedenen
dc.contributor.institutionUniv Geneva, CMU, Dept Neurosci, Geneva, Switzerlanden
dc.contributor.institutionPeking Univ, Ctr Heart, Peoples Hosp, Beijing 100871, Peoples R Chinaen
dc.contributor.institutionRoyal Infirm Edinburgh NHS Trust, Dept Cardiol, Edinburgh, Midlothian, Scotlanden
dc.contributor.institutionUniv Calif San Diego, Dept Med & Bioengn, La Jolla, CA 92093 USAen
kaust.authorCannistraci, Carloen
kaust.authorRavasi, Timothyen
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