Short-term effects of fluvastatin therapy on plasma interleukin-10 levels in patients with chronic heart failure

Coron Artery Dis. 2008 Nov;19(7):513-9. doi: 10.1097/MCA.0b013e32830d27d2.

Abstract

Background: Experimental data demonstrated that inflammatory mediators, such as pro-inflammatory and anti-inflammatory cytokines and their receptors might have important role in the development and the progression of heart failure (HF). Statins were shown to downregulate inflammatory cytokines in HF. Interleukin (IL)-10 is one of the most important anti-inflammatory cytokines. The effect of statin therapy on plasma IL-10 levels is not known in patients with HF. We conducted this study to investigate the effects of fluvastatin therapy on plasma IL-10 cytokine concentration in patients with HF.

Methods: A total of 29 patients with ischemic HF were included in this prospective uncontrolled study. Patients were assigned to fluvastatin (80 mg/day) after baseline examinations. Determination of biochemical parameters including lipids, IL-10, and tumor necrosis factor-alpha were performed at baseline and 12 weeks after the initiation of fluvastatin therapy. All participants also underwent symptom-limited exercise tolerance test at baseline and 12 weeks, and heart rate recovery (HRR) was calculated.

Results: A significant elevation in the plasma levels of IL-10 after 12 weeks of fluvastatin treatment (4.8+ or -1.0 vs. 6.5+ or -1.3 pg/ml, P=0.002) was observed. Plasma tumor necrosis factor-alpha levels were significantly decreased after fluvastatin therapy (6.3+ or -2.3 vs. 4.8+ or -1.4 pg/ml, P=0.003). Fluvastatin therapy significantly improved HRR at 1 min after 12 weeks compared with baseline (19+ or -7 vs. 24+ or -9 bpm, P<0.001). A positive correlation between the change in the levels of IL-10 and the change in HRR at 1 min (r=0.57, P<0.001) was observed.

Conclusion: Fluvastatin therapy might lead to an increase in plasma IL-10 levels and an associated improvement in vagal tonus as assessed by HRR at 1 min in patients with HF. These findings might partly explain the possible benefit observed in statin trials.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Chronic Disease
  • Fatty Acids, Monounsaturated / therapeutic use*
  • Female
  • Fluvastatin
  • Heart Failure / drug therapy*
  • Heart Failure / immunology
  • Heart Failure / physiopathology
  • Heart Rate / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Indoles / therapeutic use*
  • Interleukin-10 / blood*
  • Male
  • Middle Aged
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood
  • Up-Regulation

Substances

  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • IL10 protein, human
  • Indoles
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Fluvastatin