title: Whole body energy expenditure protein breakdown and polyamine excretion during high dose treatment with interleukin-2 and interferon-alpha.
abstract: OBJECTIVE
  To correlate changes in whole body resting energy expenditure and protein breakdown with the production of stress hormones, excretion of polyamines, and circulating concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha), in patients undergoing treatment with high doses of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha).
  
  
  METHODS
  Prospective open study.
  
  
  METHODS
  University Department of Surgery.
  
  
  METHODS
  11 Patients with malignant melanoma (n = 8) or renal cell carcinoma (n = 3) all of whom had a Karnofsky score of 80 or more.
  
  
  METHODS
  Daily intravenous infusion of IL-2 (18 x 10(6) IU/m2/day) and subcutaneous injection of IFN-alpha (3 x 10(6) IU/m2/day) for days 1-5 and 8-12 in two courses with a three week interval.
  
  
  METHODS
  Energy expenditure measured by indirect calorimetry, body temperature, heart rate, urinary excretion of amino acids and nitrogen, and plasma cytokine concentrations.
  
  
  RESULTS
  Three patients had a partial response. IL-1 was not detectable in plasma; and concentrations of IL-2 increased rapidly during the infusion before falling rapidly when it stopped, of IL-6 increased significantly (mean (SEM) 3.44 (1.6) to 11 (2) U/ml, p < 0.05), and of TNF-alpha increased by 295% (p < 0.05). Resting energy expenditure increased from 92 (4) to 113 (4) kJ/kg/day (p < 0.001) during the infusion and this was accompanied by a rise in temperature and an increase in the urinary excretion of cortisol (which also correlated with increased breakdown of whole body protein).
  
  
  CONCLUSIONS
  The increased energy expenditure and protein breakdown were probably a result of stimulation of production of catecholamines and cortisol, as after injury, but the direct effects on temperature regulating neurons may be important.
authors.affiliation: Department of Surgery, University of Göteborg, Sahlgrenska Hospital, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Naredi
authors.forename: L
authors.initials: L
authors.lastname: Hafström
authors.forename: H
authors.initials: H
authors.lastname: Zachrisson
authors.forename: C M
authors.initials: CM
authors.lastname: Rudenstam
authors.forename: K
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000628:therapy; D016207:Cytokines / Q000097:blood*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000628:therapy; D008762:Methylhistidines / Q000652:urine; D008875:Middle Aged; D011446:Prospective Studies; D011700:Putrescine / Q000652:urine; D011994:Recombinant Proteins; D013095:Spermidine / Q000652:urine
chemical_list: D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D008762:Methylhistidines; D011994:Recombinant Proteins; D013095:Spermidine; D011700:Putrescine