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Cellular endotoxin desensitization in patients with severe chronic heart failure
Author(s) -
Sharma Rakesh,
Bolger Aidan P.,
Rauchhaus Mathias,
Haehling Stephan,
Doehner Wolfram,
Adcock Ian M.,
Barnes Peter J.,
PooleWilson Philip A.,
Volk HansDieter,
Coats Andrew J.S.,
Lim Sam,
Anker Stefan D.
Publication year - 2005
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2004.09.014
Subject(s) - medicine , heart failure , desensitization (medicine) , peripheral blood mononuclear cell , tumor necrosis factor alpha , cytokine , lipopolysaccharide , receptor antagonist , interleukin 6 , circulatory system , antagonist , heart disease , gastroenterology , endocrinology , immunology , receptor , in vitro , biochemistry , chemistry
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‐α) 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‐α 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‐α 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‐α 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.