Elevated circulating IL-32 presents a poor prognostic outcome in patients with heart failure after myocardial infarction

Background: Interleukin-32 (IL-32) is a newly discovered proinflammatory cytokine. However, there are limited data regarding IL-32 as a biomarker for heart failure (HF). In this study, we assessed the prognostic value of IL-32 in patients with chronic HF after myocardial infarction (MI). Methods and results: Over a period of 1.8 years, we prospectively enrolled 100 patients with chronic HF after MI. IL-32, NT-proBNP, Matrix metallopeptidase 9 (MMP-9), procollagen type I (PI) and type III (PIII) were measured at baseline. Study endpoint was adverse cardiac events. High IL-32 levels were associated with numerous factors that are related to deteriorate cardiac function and cardiac fibrosis. Strong expression of IL-32 was detected in human cardiomyocytes from HF tissue. ROC curve revealed the area under the curve of IL-32 for predicting negative outcome of HF was 0.72 (95% CI: 0.60-0.83, P < 0.01). Kaplan-Meier statistics showed that the risk of adverse cardiac event was 5.75 fold (hazard ratio 5.75, 95% CI 1.53-21.58, P = 0.009), which increased in the highest quartile (> 296 pg/mL). Cox regression analysis revealed IL-32 was an independent predictor for cardiac events (hazard ratio 2.78, 95% CI 1.02-7.57, P = 0.046). Recombinant IL-32 significantly exacerbated infarct size in a mouse model of MI. IL-32 upregulated expression of MMP-9, PIII and transforming growth factor beta in rat fibroblasts. Conclusion: IL-32 might be a novel predictor of adverse cardiac event in patients with HF after MI. The pro-fibrotic effect of IL-32 may contribute to adverse cardiac remodeling and progression to HF. (C) 2017 Elsevier B.V. All rights reserved.