Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure.
OBJECTIVE
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.
Gielen
Stephan
S
Universität Leipzig, Herzzentrum GmbH, Department of Internal Medicine & Cardiology, Strümpellstrasse 39, 04289 Leipzig, Germany.
Adams
Volker
V
Möbius-Winkler
Sven
S
Linke
Axel
A
Erbs
Sandra
S
Yu
Jiangtao
J
Kempf
Werner
W
Schubert
Andreas
A
Schuler
Gerhard
G
Hambrecht
Rainer
R
D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005081:Exercise Therapy / Q000379:methods* / Q000592:standards; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000534:rehabilitation*; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000032:analysis* / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000032:analysis* / Q000097:blood; D010101:Oxygen Consumption; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000378:metabolism; D019282:Wasting Syndrome / Q000209:etiology
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase