title: Albumin synthesis rates are not decreased in hypoalbuminemic cachectic cancer patients with an ongoing acute-phase protein response.
abstract: OBJECTIVE
  To determine whether suppression of albumin synthesis contributes to the hypoalbuminemia observed in weight-losing cancer patients with evidence of an ongoing acute-phase protein response (APPR).
  
  
  BACKGROUND
  Proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are known to downregulate albumin synthesis and increase acute-phase protein production in isolated hepatocytes. However, whether albumin synthesis is suppressed in hypoalbuminemic cancer patients with evidence of an ongoing acute-phase response is unknown.
  
  
  METHODS
  Albumin synthesis rates were determined in six healthy controls and in six weight-losing pancreatic cancer patients with an ongoing APPR using a flooding dose technique with [2H5]-phenylalanine. The presence of an APPR was defined as a serum C-reactive protein concentration >10 mg/L. Serum cytokines (TNF, IL-6) and soluble TNF receptors (sTNF-R 55 and 75), along with serum cortisol and insulin, were also measured in both groups.
  
  
  RESULTS
  Cancer patients had reduced serum albumin (median 32 [range, 23-36] vs. 42 g/L [40-45]; p < 0.01) and increased serum C-reactive protein concentrations (72 [23-126] vs. <5 mg/L; p < 0.01) when compared with controls. TNF was not detected in either group. sTNF-R 55 levels were significantly elevated in the cancer patients (3.8 [1.9-8.1] vs. 1.2 pg/mL [0.9-2.2]; p < 0.01). Circulating IL-6, insulin, and cortisol concentrations were not significantly different between the groups. The intravascular albumin mass was lower (88 [56-93] vs. 133 g [105-177]; p < 0.01), but the intravascular albumin fractional synthetic rate was higher (13.9 [13.5-18.5] vs. 10.3%/d [71-11.3]; p < 0.01) in the cancer patients compared with the controls. The total intravascular albumin synthetic rate was, however, similar between the two groups (12.7 [7.7-15.7] vs. 11.7 g/d [8.5-18.7]; p NS).
  
  
  CONCLUSIONS
  In weight-losing pancreatic cancer patients with evidence of an ongoing APPR, hypoalbuminemia is not caused by a decreased rate of albumin synthesis.
authors.affiliation: University Department of Surgery, Royal Infirmary, Edinburgh, United Kingdom.
authors.forename: K C
authors.initials: KC
authors.lastname: Fearon
authors.forename: J S
authors.initials: JS
authors.lastname: Falconer
authors.forename: C
authors.initials: C
authors.lastname: Slater
authors.forename: D C
authors.initials: DC
authors.lastname: McMillan
authors.forename: J A
authors.initials: JA
authors.lastname: Ross
authors.forename: T
authors.initials: T
authors.lastname: Preston
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000210:Acute-Phase Reaction / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D000368:Aged; D000418:Albumins / Q000096:biosynthesis*; D002100:Cachexia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D010953:Plasma Volume; D012709:Serum Albumin / Q000032:analysis
chemical_list: D000209:Acute-Phase Proteins; D000418:Albumins; D016207:Cytokines; D012709:Serum Albumin