The role of temporal changes of pro-inflammatory cytokines in the development of adverse cardiac remodeling after ST-elevation myocardial infarction.

ABSTRACT

Introduction: Increasing evidence supports the view that pro-inflammatory cytokines play a role in fibrosis after myocardial infarction (MI). It has been suggested that interleukin (IL)-12p40, a pro-inflammatory cytokine, can induce interferon γ (IFN-γ) and matrix metalloproteinase (MMP). However, the role of IL-12p40 in adverse cardiac remodeling (AR) after ST-elevation MI (STEMI) is unclear. Aim: To examine the role of temporal changes of pro-inflammatory cytokines in the development of post-STEMI AR. Material and methods: A total of 43 patients with STEMI for the first time ever were prospectively analyzed. In cardiac magnetic resonance imaging at 6 months after STEMI, a decrease of left ventricular end-diastolic volume by ≥ 12% was defined as reverse cardiac remodeling (RR), and a 12% increase was defined as AR. Cytokine concentrations were measured on the first day (baseline) and 2 weeks after STEMI. Results: Mean IL-12p40 (59.1 ±14.5 vs. 46.7 ±9.1 pq/ml, p = 0.001), median IFN-γ (20.4 vs. 16.2 pq/ml, p = 0.048) and median MMP-2 (33866 vs. 20691 pq/ml, p = 0.011) baseline concentrations were higher in AR than RR. In patients with AR, IL-12p40 level was lower at 2 weeks than baseline (p < 0.001). There was a positive correlation between the baseline concentrations of IL-12p40, IFN-γ, MMP-2, C-reactive protein and infarct size (p < 0.05). Increased IL-12p40 and MMP-2 baseline levels were independently associated with AR (OR = 1.14, p = 0.010; OR = 1.08, p = 0.035). Conclusions: In the initial phase of MI, greater release of pro-inflammatory cytokines was associated with increased MMP-2 levels. Elevated expression of IL-12 and MMP-2 had an independent association with AR. This may be related to the excessive inflammatory response in the initial phase of MI.