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)
Acute myocardial infarction, Bioengineering, Inflammation, Computational and systems biology, Cytokines, Interleukin-6, Interleukin-10
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
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
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
stratification and immune-modulating
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