© 2006 European Society of Cardiology
The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure
a Clinical Cardiology, National Heart and Lung Institute, Imperial College School of Medicine London, UK
b Department of Medicine II, Johannes Gutenberg-University Mainz, Germany
c Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School, Humboldt University Berlin, Germany
d Institute of Medical Immunology, Charité Medical School, Humboldt-University Berlin, Germany
* Corresponding author. Department of Medicine II, Johannes Gutenberg-University, Langenbeckstraße 1, 55131 Mainz, Germany. Tel.: +49 6131 173747; fax: +49 6131 176613. E-mail address: genth{at}2-med.klinik.uni-mainz.de
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Abstract |
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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.
Key Words: Immunactivation • CHF • CD14 antibody • TNF inhibition
Received November 29, 2004; Revised August 2, 2005; Accepted October 13, 2005