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-α) 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 64α9.1 years, all NYHA class II, eight male) and incubated for 6 h, the TNF-α production being measured. Serum lipoproteins were quantified using standard techniques. In CHF patients, there was an inverse relationship between whole blood TNF-α 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-α production ex vivo.