title: Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6- interleukin-10+ cytokine patterns in ST-elevation acute myocardial infarction.
abstract: BACKGROUND
  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.
  
  
  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-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-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.
authors.affiliation: Clinical Cardiovascular Biology Centre. ammirati.enrico@hsr.it
authors.forename: Enrico
authors.initials: E
authors.lastname: Ammirati
authors.forename: Carlo V
authors.initials: CV
authors.lastname: Cannistraci
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Cristell
authors.forename: Viviana
authors.initials: V
authors.lastname: Vecchio
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Palini
authors.forename: Per
authors.initials: P
authors.lastname: Tornvall
authors.forename: Anna M
authors.initials: AM
authors.lastname: Paganoni
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Miendlarzewska
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sangalli
authors.forename: Alberto
authors.initials: A
authors.lastname: Monello
authors.forename: John
authors.initials: J
authors.lastname: Pernow
authors.forename: Marie
authors.initials: M
authors.lastname: Björnstedt Bennermo
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Marenzi
authors.forename: Dayi
authors.initials: D
authors.lastname: Hu
authors.forename: Neal G
authors.initials: NG
authors.lastname: Uren
authors.forename: Domenico
authors.initials: D
authors.lastname: Cianflone
authors.forename: Timothy
authors.initials: T
authors.lastname: Ravasi
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.forename: Attilio
authors.initials: A
authors.lastname: Maseri
mesh_terms: D000368:Aged; D000465:Algorithms; D001185:Artificial Intelligence; D016000:Cluster Analysis; D004562:Electrocardiography; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality*; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D015398:Signal Transduction / Q000276:immunology; D013599:Systole / Q000276:immunology
chemical_list: C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016753:Interleukin-10