The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure

Sabine Genth-Zotz, Stephan von Haehling, Aidan P. Bolger, Paul R. Kalra, Roland Wensel, Andrew J S Coats, Hans Dieter Volk, Stefan D. Anker

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)366-372
Number of pages7
JournalEuropean Journal of Heart Failure
Volume8
Issue number4
DOIs
Publication statusPublished - Jun 2006

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Endotoxins
Anti-Idiotypic Antibodies
Heart Failure
Tumor Necrosis Factor-alpha
CD14 Antigens
Healthy Volunteers

Keywords

  • CD14 antibody
  • CHF
  • Immunactivation
  • TNF inhibition

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure. / Genth-Zotz, Sabine; von Haehling, Stephan; Bolger, Aidan P.; Kalra, Paul R.; Wensel, Roland; Coats, Andrew J S; Volk, Hans Dieter; Anker, Stefan D.

In: European Journal of Heart Failure, Vol. 8, No. 4, 06.2006, p. 366-372.

Research output: Contribution to journalArticle

Genth-Zotz, Sabine ; von Haehling, Stephan ; Bolger, Aidan P. ; Kalra, Paul R. ; Wensel, Roland ; Coats, Andrew J S ; Volk, Hans Dieter ; Anker, Stefan D. / The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure. In: European Journal of Heart Failure. 2006 ; Vol. 8, No. 4. pp. 366-372.
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abstract = "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.",
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