Identification and Predictive Value of IL6(+)IL10(+) and IL6(-)IL10(+) Cytokine Patterns in ST-Elevation Acute Myocardial Infarction

Rationale: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very elevated circulating interleukin IL6(+)levels or very low IL6(-)levels. Objective: We compared these two 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 IL6 level (median 15.6 pg/ml; IL6(+)STEMI) with 96 in the bottom IL6 level (median 1.7 pg/ml; IL6(-)STEMI) and 103 matched controls extracted from the multi-ethnic First Acute Myocardial Infarction Study. We found minimal clinical differences between the IL6(+)STEMI and IL6(-)STEMI. We assessed the inflammatory profiles of the two 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. IL6(+)STEMI patients were characterized by the activation of two modules of interacting signals comprising (a)IL10, IL8, MIP1α and C-reactive protein and (b)MCP1, MIP1β and MIG. IL10 was increased both in IL6(+)STEMI and IL6(-)STEMI patients compared with controls. IL6(+)IL10(+)STEMI patients had an increased risk of systolic dysfunction at discharge and of death at six months in comparison with IL6(-)IL10(+)STEMI patients. We combined IL10 and MIG (derived from the two identified cytokine modules) with IL6 in a formula yielding a risk-index that outperformed any single cytokine in prediction of systolic dysfunction and death. Conclusions: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients that is not related to the extent of the myocardial damage. The simultaneous elevation of IL6 and IL10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and for immune-modulating therapies.