Cellular endotoxin desensitization in patients with severe chronic heart failure

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-alpha) 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 I I healthy controls (mean age 53 +/- 3 years, age range 39 to 75 years) were separated frorn venous blood and Cultured for 24 It with LPS (E, coli, 0-10 ng/mL). Culture supernatants were tested for TNF-alpha and interleukin receptor antagonist (IL- IRA). Patients were subgrouped into mild (n=1 0), moderate (n=5), and severe (n=9) CHF. Independently of age, rnononuclear cells from patients with severe heart failure produced less TNF-alpha than controls (p < 0.05) and patients with mild (p < 0.001) or moderate CHF (p < 0.05). IL- I RA 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-a 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. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.