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.