title: Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511 single nucleotide polymorphism.
abstract: BACKGROUND
  Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response.
  
  
  OBJECTIVE
  We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients.
  
  
  METHODS
  A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and compared with healthy control subjects (HCs). Body composition was determined by bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of interleukin 1beta (IL-1beta -511), IL-6 (IL-6 -174), and the tumor necrosis factor system (TNF-alpha -308 and lymphotoxin-alpha +252) were determined. Plasma C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured.
  
  
  RESULTS
  Fat mass, leptin, and pseudouridine were significantly different (P < 0.001) between noncachectic patients (NCPs) and cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was not. NCPs had a body compositional shift toward a lower fat-free mass and a higher fat mass compared with HCs. CPs and NCPs had a greater systemic inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of the IL-1beta -511 polymorphism was significantly different between the groups (P < 0.05).
  
  
  CONCLUSIONS
  In COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.
authors.affiliation: Department of Respiratory Medicine, University Hospital Maastricht, The Netherlands. r.broekhuizen@pul.unimaas.nl
authors.forename: Roelinka
authors.initials: R
authors.lastname: Broekhuizen
authors.forename: Robert F
authors.initials: RF
authors.lastname: Grimble
authors.forename: W Martin
authors.initials: WM
authors.lastname: Howell
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Shale
authors.forename: Eva C
authors.initials: EC
authors.lastname: Creutzberg
authors.forename: Emiel F
authors.initials: EF
authors.lastname: Wouters
authors.forename: Annemie M
authors.initials: AM
authors.lastname: Schols
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002100:Cachexia / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D017097:Electric Impedance; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011560:Pseudouridine / Q000652:urine; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D011560:Pseudouridine; D002097:C-Reactive Protein