© 2005 European Society of Cardiology
Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins
a Clinical Cardiology, NHLI, Imperial College School of Medicine Dovehouse Street, SW3 6LY, London, UK
b Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School Berlin, Germany
c Department of Medicine II, Johannes Gutenberg-University Mainz, Germany
d Thoracic Medicine, NHLI, Imperial College School of Medicine London, UK
e Department of Clinical Immunology, Charité Campus Mitte, Berlin, Germany
* Corresponding:author. Department of Clinical Cardiology National Heart and Lung Institute Dovehouse Street, London, SW3 6LY, UK. Tel.: +44 020 7351 8203; Fax: +44 020 7351 8733. E-mail address: s.anker{at}imperial.ac.uk
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Abstract |
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Background: Endotoxin [lipopolysaccharide (LPS)] may be an important stimulus for cytokine release in patients with chronic heart failure (CHF). We sought to investigate the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations. It is not known if low-dose LPS is sufficient to stimulate immune activation.
Methods and results: Whole blood from 32 CHF patients (mean age 66±2 years, NYHA class 2.7±0.2, five female) and 11 healthy control subjects (mean age 47±4 years, six female) was stimulated with LPS at nine different concentrations (0.001 to 10 ng/mL), and tumor necrosis factor (TNF-
) release was quantified. Reference standard endotoxin at concentrations of 0, 0.6, 1, and 3 EU/ml was added to whole blood from nine CHF patients (age 649.1 years, all NYHA class II, eight male) and incubated for 6 h, the TNF- production being measured. Serum lipoproteins were quantified using standard techniques. In CHF patients, there was an inverse relationship between whole blood TNF- release and serum cholesterol which was strongest at 0.6 ng/mL of LPS (r=–0.53, p=0.002). A similar although weaker relationship was found for serum HDL. No such correlation was found in healthy subjects or with serum LDL (all r2<0.1). Low concentrations of LPS induced a stepwise increase in TNF-± release from whole blood to concentrations well above those seen in CHF.
Conclusions: Serum lipoproteins may play an important role in regulating LPS bioactivity in CHF. Very low LPS activity, at levels seen in vivo in CHF, can induce significant TNF- production ex vivo.
Key Words: Heart failure • Immune system • Lipids • Lipopolysaccharide
Received January 5, 2004; Revised August 12, 2004; Accepted September 20, 2004
1 Rakesh Sharma, Stephan von Haehling, Mathias Rauchhaus and Aidan P. Bolger contributed equally to the work in this manuscript.
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