© 2004 European Society of Cardiology
Cellular endotoxin desensitization in patients with severe chronic heart failure
a Clinical Cardiology, NHLI Imperial College School of Medicine, London, UK
b Division of Applied Cachexia Research Department of Cardiology, Charité Medical School, Berlin, Germany
c Thoracic Medicine, NHLI Imperial College School of Medicine, London, UK
d Department of Clinical Immunology Charité Campus Mitte, Berlin, Germany
* Corresponding author. Department of Clinical Cardiology, National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, UK. Tel.: +44 20 7351 8203; fax: +44 20 7351 8733. E-mial address: s.anker{at}imperial.ac.uk
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Abstract |
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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-
) production which does not affect other cytokine parameters. It is not known if LPS desensitization occurs in CHF.
Methods and 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- 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- 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- 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.
Key Words: Heart failure • Lipopolysaccharide • Cytokines
Received January 5, 2004; Revised June 8, 2004; Accepted September 20, 2004
1 Rakesh Sharma, Aidan P. Bolger, Mathias Rauchhaus and Stephan von Haehling contributed equally to the work in this manuscript.