title: Cellular endotoxin desensitization in patients with severe chronic heart failure.
abstract: BACKGROUND
  Increased levels of bacterial lipopolysaccharide (LPS) have been demonstrated in chronic heart failure (CHF). LPS can induce cellular desensitization, with specific down-regulation of LPS-mediated cellular tumor necrosis factor (TNF-alpha) production which does not affect other cytokine parameters. It is not known if LPS desensitization occurs in CHF.
  
  
  RESULTS
  Mononuclear cells from 24 CHF patients (mean age 70+/-2 years, age range 58 to 78 years, NYHA class 3.0+/-0.2) and 11 healthy controls (mean age 53+/-3 years, age range 39 to 75 years) were separated from venous blood and cultured for 24 h with LPS (E. coli, 0-10 ng/mL). Culture supernatants were tested for TNF-alpha and interleukin-1 receptor antagonist (IL-1RA). Patients were subgrouped into mild (n=10), moderate (n=5), and severe (n=9) CHF. Independently of age, mononuclear cells from patients with severe heart failure produced less TNF-alpha than controls (p<0.05) and patients with mild (p<0.001) or moderate CHF (p<0.05). IL-1RA release was higher for CHF patients as a group, compared with controls (p<0.05). There was no significant difference in IL-1RA release between CHF patient subgroups.
  
  
  CONCLUSIONS
  Mononuclear cells from patients with severe heart failure produce significantly less TNF-alpha than healthy controls or patients with mild to moderate disease. Production of IL-1RA is not affected. This resembles a picture indicative of LPS desensitization occurring in patients with severe CHF.
authors.affiliation: Clinical Cardiology, NHLI, Imperial College School of Medicine, London, UK.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Aidan P
authors.initials: AP
authors.lastname: Bolger
authors.forename: Mathias
authors.initials: M
authors.lastname: Rauchhaus
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: Philip A
authors.initials: PA
authors.lastname: Poole-Wilson
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.forename: Sam
authors.initials: S
authors.lastname: Lim
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha