title: Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting.
abstract: OBJECTIVE
  We sought to assess the possible relations between clinical severity of chronic heart failure and catabolic factors, specifically tumor necrosis factor (TNF), soluble TNF receptors 1 and 2 (sTNFR-1 and sTNFR-2), cortisol, testosterone and dehydroepiandrosterone (DHEA).
  
  
  BACKGROUND
  Chronic heart failure is associated with loss of muscle bulk that may be related to alteration of the balance between catabolism and anabolism.
  
  
  METHODS
  Sixty-three patients (average age +/- SD 60.4 +/- 11.3 years) with stable chronic heart failure and 20 control subjects aged 52.8 +/- 11.4 years were studied. We measured body mass index (BMI) and obtained maximal incremental exercise testing with metabolic gas exchange measurements and measurements of venous levels of TNF, sTNFR-1 and sTNFR-2, cortisol and DHEA.
  
  
  RESULTS
  There was no difference in total TNF-alpha levels between patients and control subjects (9.76 +/- 8.59 vs. 6.84 +/- 2.7 pg/ml). sTNFR-1 (128.9 +/- 84.5 vs. 63.6 +/- 23.3 pg/ml, p < 0.003) and sTNFR-2 (250.1 +/- 109.5 vs. 187.9 +/- 92.2 pg/ml, p = 0.03) were higher in patients. DHEA was lower in patients (9.88 +/- 6.94 vs. 15.64 +/- 8.33 nmol/liter, p = 0.004). The ratio of log cortisol to log DHEA correlated with log TNF level (r = 0.50, p < 0.001 for the patients alone; r = 0.48, p < 0.001 for the group as a whole). Peak oxygen consumption correlated with both sTNFR-1 and sTNFR-2 (r = -0.51, p < 0.001 and r = -0.39, p < 0.001, respectively). There was a negative correlation between BMI and TNF levels (r = -0.43, p < 0.001 for the patients) and the cortisol/DHEA ratio (r = -0.32, p = 0.01 for the patients).
  
  
  CONCLUSIONS
  There is an increase in TNF and its soluble receptors in chronic heart failure. This increase is associated with a rise in the cortisol/DHEA (catabolic/anabolic) ratio. These changes correlate with BMI and clinical severity of heart failure, suggesting a possible etiologic link.
authors.affiliation: Department of Cardiac Medicine, National Heart and Lung Institute, London, England.
authors.forename: S D
authors.initials: SD
authors.lastname: Anker
authors.forename: A L
authors.initials: AL
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Kemp
authors.forename: C
authors.initials: C
authors.lastname: Salsbury
authors.forename: M M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: P G
authors.initials: PG
authors.lastname: Hellewell
authors.forename: A J
authors.initials: AJ
authors.lastname: Coats
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D005080:Exercise Test; D006333:Heart Failure / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008875:Middle Aged; D009133:Muscular Atrophy / Q000209:etiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012720:Severity of Illness Index; D013739:Testosterone / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019282:Wasting Syndrome / Q000209:etiology*
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone