Endotoxin sensitivity and immune competence in chronic heart failure

Abstract

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 TNFα 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. TNFα 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 TNFα 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.