title: Endotoxin hypersensitivity in chronic heart failure.
abstract: BACKGROUND
  Raised concentrations of endotoxin (lipopolysaccharides, LPS) have been demonstrated in patients with chronic heart failure (CHF). Tolerance of monocytes to LPS can be induced by negative feedback mechanism through LPS itself, resulting in a downregulation of cytokine response to LPS challenge. As endotoxin desensitization has also been suggested for CHF, we investigated the response to LPS challenge in CHF patients.
  
  
  METHODS
  We prospectively studied 100 patients with CHF (62 +/- 13 years) and 21 controls (58 +/- 10 years, LVEF 60 +/- 3%). HLA-DR expression and TNFalpha generation of monocytes after ex vivo stimulation by LPS (stimulation with LPS 50 and 500 pg/ml) were determined. 46 CHF patients were in NYHA class II (LVEF 29 +/- 8%) and 54 in NYHA class III (LVEF 27 +/- 7%).
  
  
  RESULTS
  HLA-DR expression in controls (25,837 +/- 7915 ABS/cell) was comparable to CHF NYHA II patients (23,720 +/- 8488 ABS/cell, n.s.), but lower in patients classified NYHA III (20,327 +/- 5073 ABS/cell, p < 0.01). Stimulated TNFalpha production ex vivo was higher in CHF NYHA III (LPS 50: 437 +/- 284; LPS 500: 946 +/- 500 pg/ml, each p < 0.05) and CHF NYHA II (LPS 50: 397 +/- 277; LPS 500: 933 +/- 483 pg/ml, each p < 0.05) compared to controls (LPS 50: 315 +/- 134; LPS 500: 715 +/- 339 pg/ml).
  
  
  CONCLUSIONS
  In chronic heart failure TNFalpha generation capacity increases while HLA-DR expression decreases compared to controls. Thus patients with CHF display enhanced susceptibility to inflammatory stimuli.
authors.affiliation: Medical Clinic I, University Hospital, University of Technology, Aachen, Germany. s.krueger@uniklinik-ulm.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kunz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Graf
authors.forename: Tina
authors.initials: T
authors.lastname: Stickel
authors.forename: Marc W
authors.initials: MW
authors.lastname: Merx
authors.forename: Karl Christian
authors.initials: KC
authors.lastname: Koch
authors.forename: Uwe
authors.initials: U
authors.lastname: Janssens
authors.forename: Peter
authors.initials: P
authors.lastname: Hanrath
mesh_terms: D000368:Aged; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000150:complications*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D008070:Lipopolysaccharides