Identification and predictive value of Interleukin-6+ Interleukin-10+ and Interleukin-6- Interleukin-10+ Cytokine Patterns in ST-Elevation acute myocardial infarction

A. Ammirati, C.V. Cannistraci, N.A. Cristell, V. Vecchio, A.G. Palini, P. Tornvall, A.M. Paganoni, E.A. Miendlarzewska, L.M. Sangalli, A. Monello, J. Pernow, M. Bjornstedt Bennermo, G. Marenzi, D. Hu, N.G. Uren, D. Cianflone, T. Ravasi, A.A. Manfredi, A.
Circ Res., 111(10):1336-48, (2012)

Identification and predictive value of Interleukin-6+ Interleukin-10+ and Interleukin-6- Interleukin-10+ Cytokine Patterns in ST-Elevation acute myocardial infarction

Keywords

Acute myocardial infarction, Bioengineering, Inflammation, Computational and systems biology, Cytokines, Interleukin-6, Interleukin-10

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-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.

Code

DOI: 10.1161/CIRCRESAHA.111.262477                                    

Sources

Website PDF

See all publications 2012