Circulating Levels of IL-6 Receptor and gp130 and Long-Term Clinical Outcomes in ST-Elevation Myocardial Infarction.

BACKGROUND: Reports on soluble interleukin-6 (IL-6) receptor (sIL-6R) and glycoprotein 130 (sgp130) in ST-elevation myocardial infarction (STEMI) are few and include a small number of patients. The aim of this study was to investigate the possible association between levels of these biomarkers in the acute phase of STEMI and future cardiovascular events. METHODS AND RESULTS: Circulating IL-6, sgp130, sIL-6R, and C-reactive protein (CRP) were measured in 989 STEMI patients during 2007-2011, and cardiovascular events were recorded during follow-up. The primary endpoint was composite of all-cause mortality, myocardial infarction, stroke, unscheduled revascularization, or rehospitalization for heart failure. Cox regression models were used to estimate hazard ratios (HRs) for cardiovascular events in relation to biomarker levels. Median levels of sIL-6R, sgp130, IL-6, and CRP measured 24 hours (median) after symptom onset were 39.2 ng/mL, 240 ng/mL, 18.8 pg/mL, and 13.7 mg/L, respectively. During a median follow-up time of 4.6 years, 200 patients (20.2%) experienced a primary endpoint, and 82 patients (8.3%) died. Patients with sIL-6R levels in the upper quartile (>47.7 ng/mL) had significantly higher risk of future adverse events (primary endpoint) and mortality compared to patients with lower levels (adjusted HR, 1.54 [1.08, 2.21]; P=0.02 and 1.81 [1.04, 3.18]; P=0.04, respectively). Neither IL-6 nor sgp130 levels were related to future events, but patients with CRP levels in the upper quartile (>31.5 mg/L) had higher risk of death. CONCLUSION: High levels of sIL-6R were associated with future cardiovascular events and mortality in STEMI patients, suggesting an important role of the IL-6 signaling system.

IL-6 signalling in patients with acute ST-elevation myocardial infarction.

Cytokines of the IL-6 family have been related to infarct size and prognosis in patients with myocardial infarction. The aims of the present study were to elucidate possible associations between myocardial necrosis and left ventricular impairment and members of the IL-6 transsignalling system including soluble (s) IL-6R and (s) glycoprotein 130 (sgp130) in patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. In blood samples from 1028 STEMI patients, collected in-hosptial, we found significant correlations between peak TnT and IL-6 and CRP (p < 0.001, all) and between IL-6 and CRP and LV ejection fraction and NT-proBNP (p < 0.001, all). On the contrary, no significant associations were found between peak TnT and sgp130 or sIL-6R. Furthermore sgp130 was significantly elevated in diabetic patients and also associated with the glucometabolic state. In conclusion, circulating levels of IL-6 and CRP, but not the soluble forms of the receptor (sIL-6R) or the receptor signalling subunit (sgp130) were associated with the extent of myocardial necrosis. The biological importance of the IL-6/gp130-mediated signalling pathways in patients with acute myocardial infarction and dysglycemia should be further elucidated.