Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure

J Am Coll Cardiol. 2003 Sep 3;42(5):861-8. doi: 10.1016/s0735-1097(03)00848-9.

Abstract

Objectives: The aim of this study was to assess the effects of regular physical exercise on local inflammatory parameters in the skeletal muscle of patients with chronic heart failure (CHF).

Background: Inflammatory activation with increased serum cytokine levels and expression of inducible nitric oxide synthase (iNOS) in the myocardium and peripheral skeletal muscles has been described in CHF.

Methods: Twenty male patients with stable CHF (left ventricular ejection fraction 25 +/- 2%; age 54 +/- 2 years) were randomized to a training group (n = 10) or a control group (n = 10). At baseline and after six months, serum samples and vastus lateralis muscle biopsies were obtained. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1-beta levels were measured by enzyme-linked immunosorbent assay, local cytokine, and iNOS expression by real-time polymerase chain reaction.

Results: Exercise training improved peak oxygen uptake by 29% in the training group (from 20.3 +/- 1.0 to 26.1 +/- 1.5 ml/kg. min; p < 0.001 vs. control group). While serum levels of TNF-alpha, IL-6, and IL-1-beta remained unaffected by training, local skeletal muscle TNF-alpha decreased from 1.9 +/- 0.4 to 1.2 +/- 0.3 relative U (p < 0.05 for change vs. control group), IL-6 from 71.3 +/- 16.5 to 41.3 +/- 8.8 relative U (p < 0.05 vs. begin), and IL-1-beta from 2.7 +/- 1.1 to 1.4 +/- 0.6 relative U (p = 0.02 vs. control group). Exercise training also reduced local iNOS expression by 52% (from 6.3 +/- 1.2 to 3.0 +/- 1.0 relative U; p = 0.007 vs. control group).

Conclusions: Exercise training significantly reduced the local expression of TNF-alpha, IL-1-beta, IL-6, and iNOS in the skeletal muscle of CHF patients. These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Case-Control Studies
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Exercise Therapy / methods*
  • Exercise Therapy / standards
  • Heart Failure / complications
  • Heart Failure / diagnosis
  • Heart Failure / immunology*
  • Heart Failure / metabolism
  • Heart Failure / rehabilitation*
  • Humans
  • Inflammation
  • Interleukin-1 / analysis*
  • Interleukin-1 / blood
  • Interleukin-6 / analysis*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Muscle, Skeletal / chemistry*
  • Muscle, Skeletal / immunology*
  • Nitric Oxide Synthase / analysis*
  • Nitric Oxide Synthase / blood
  • Oxygen Consumption
  • Prospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / analysis*
  • Tumor Necrosis Factor-alpha / metabolism
  • Wasting Syndrome / etiology

Substances

  • Interleukin-1
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase