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The anti‐CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor‐alpha in patients with chronic heart failure
Author(s) -
GenthZotz Sabine,
Haehling Stephan,
Bolger Aidan P.,
Kalra Paul R.,
Wensel Roland,
Coats Andrew J.S.,
Volk HansDieter,
Anker Stefan D.
Publication year - 2006
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.2005.10.010
Subject(s) - medicine , cd14 , tumor necrosis factor alpha , heart failure , endocrinology , ex vivo , stimulation , immune system , lipopolysaccharide , receptor , in vivo , immunology , biology , microbiology and biotechnology
Background: Activation of the endotoxin (LPS) receptor, CD14, leads to tumor necrosis factor‐alpha (TNF) production. Plasma LPS activity is elevated in patients with severe chronic heart failure (CHF). An anti‐CD14 antibody, IC14, blocks TNF production in healthy volunteers. It is not known whether IC14 prevents TNF production in CHF patients. Methods and results: Blood from 20 CHF patients (age 64±2.1 years, NYHA class 2.2±0.1, LVEF 27±3%, mean±SEM) was pre‐incubated with 0.5, 1.0, 5.0, 10 and 50 μg/mL IC14 for 1 h followed by incubation with 1 or 10 ng/mL LPS for 6 h. Fourteen subjects served as controls (58±2.4 years). LPS‐stimulated TNF release was 76% and 60% greater at 1 and 10 ng/mL LPS, respectively, in CHF patients versus controls ( p =0.07 and p =0.008). IC14 at concentrations of 5.0, 10 and 50 μg/mL substantially reduced TNF production in response to stimulation with LPS (all p <0.05). CD14 receptor density was similar in patients and controls. In controls, but not in CHF patients, there was a positive correlation between CD14 receptor density and TNF production ( r =0.61, p =0.03). Conclusion: IC14 suppresses LPS‐stimulated whole blood TNF production in patients with CHF and in normal subjects and therefore may represent a novel therapeutic strategy for CHF patients with systemic immune activation.