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

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-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: Enrico Ammirati, Carlo V Cannistraci, Nicole A Cristell, Viviana Vecchio, Alessio G Palini, Per Tornvall, Anna M Paganoni, Ewa A Miendlarzewska, Laura M Sangalli, Alberto Monello, John Pernow, Marie Björnstedt Bennermo, Giancarlo Marenzi, Dayi Hu, Neal G Uren, Domenico Cianflone, Timothy Ravasi, Angelo A Manfredi, Attilio Maseri
• Journal: Circulation research (Circ Res) Vol. 111 Issue 10 Pg. 1336-48 (Oct 26 2012) ISSN: 1524-4571 [Electronic] United States
• PMID: 22931953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• IL6 protein, human
• Interleukin-6
• Interleukin-10

Topics

• Aged
• Algorithms
• Artificial Intelligence
• Cluster Analysis
• Electrocardiography
• Female
• Humans
• Interleukin-10 (blood, immunology)
• Interleukin-6 (blood, immunology)
• Male
• Middle Aged
• Myocardial Infarction (diagnosis, immunology, mortality)
• Predictive Value of Tests
• Prognosis
• ROC Curve
• Risk Factors
• Signal Transduction (immunology)
• Systole (immunology)