Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins.
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.


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-alpha) 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 64+/-9.1 years, all NYHA class II, eight male) and incubated for 6 h, the TNF-alpha production being measured. Serum lipoproteins were quantified using standard techniques. In CHF patients, there was an inverse relationship between whole blood TNF-alpha 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 r(2)<0.1). Low concentrations of LPS induced a stepwise increase in TNF-alpha 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-alpha production ex vivo.
Sharma
Rakesh
R
Clinical Cardiology, NHLI, Imperial College School of Medicine, Dovehouse Street, SW3 6LY, London, UK.
von Haehling
Stephan
S
Rauchhaus
Mathias
M
Bolger
Aidan P
AP
Genth-Zotz
Sabine
S
Doehner
Wolfram
W
Oliver
Brian
B
Poole-Wilson
Philip A
PA
Volk
Hans-Dieter
HD
Coats
Andrew J S
AJ
Adcock
Ian M
IM
Anker
Stefan D
SD
D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D008074:Lipoproteins; D014409:Tumor Necrosis Factor-alpha