Endotoxin sensitivity and immune competence in chronic heart failure.
BACKGROUND
Raised concentrations of endotoxin (lipopolysaccharide, LPS) are found in patients with chronic heart failure (CHF). Tolerance of monocytes to LPS can be induced by LPS itself resulting in a downregulation of cytokine response to LPS challenge. This phenomenon of LPS desensitization has also been suggested for CHF.


METHODS
We investigated whether CHF patients really show a desensitization to LPS stimuli at rest or after physical exercise, which was used as a model of limited inflammatory reaction. Thirty-five patients with CHF (59+/-12 years, 8 women) and 30 healthy control subjects were prospectively studied with cardiopulmonary exercise testing. At rest and directly after exercise blood samples were taken for the quantitative determination of HLA-DR expression of monocytes as a measure for immune competence and for the measurement of TNFalpha generation after ex vivo stimulation by LPS.


RESULTS
HLA-DR expression was comparable in CHF patients and controls at rest as well as after exercise. TNFalpha production by LPS-stimulated monocytes ex vivo was higher in CHF patients compared to controls at rest and after exercise.


CONCLUSIONS
Thus, our data are the first to show that patients with stable CHF show a cellular hypersensitivity to LPS with a higher TNFalpha generation capacity at rest and after exercise compared to controls. CHF patients seem to have a marked susceptibility to low inflammatory stimuli and no desensitization to LPS.
Krüger
Stefan
S
Medical Clinic I, University Hospital, University of Technology, Aachen, Germany. skrueger@ukaachen.de
Kunz
Dagmar
D
Graf
Jürgen
J
Stickel
Tina
T
Merx
Marc W
MW
Hanrath
Peter
P
Janssens
Uwe
U
D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006331:Heart Diseases / Q000097:blood / Q000276:immunology*; D006333:Heart Failure / Q000097:blood / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha