Mechanisms
Single endotoxin dose triggers rapid LDL decline and slower CETP activity loss in healthy volunteers (J Lipid Res 2003)
Original title: A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers
To probe how endotoxemia causes rapid LDL and HDL declines, six healthy volunteers received a single small intravenous dose of endotoxin (E. coli 0113, 2 ng/kg) or saline in a crossover trial. Endotoxin triggered mild flu-like symptoms and sharp rises in TNF, its soluble receptors, IL-6, cortisol, serum amyloid A, and CRP; triglycerides and VLDL-TG rose then fell (nadir at 9h), followed by declines in cholesterol, LDL cholesterol, apoB, and phospholipid (nadirs at 12-24h), while HDL cholesterol and apoA-I were unaffected even though half the phospholipid loss came from HDL. Lipopolysaccharide binding protein rose 3-fold (peak at 12h), accompanied by smaller, later decreases in phospholipid transfer protein and cholesteryl ester transfer protein activity. The authors conclude endotoxin rapidly lowers LDL and selectively strips HDL phospholipid, likely via lipopolysaccharide binding protein, a process that with more intense inflammation could reduce HDL levels.
Original abstract
Endotoxemia is associated with rapid and marked declines in serum levels of LDL and HDL by unknown mechanisms. Six normal volunteers received a single, small intravenous (iv) dose of endotoxin (Escherichia coli 0113, 2 ng/kg) or saline in a random order, cross-over design. After endotoxin treatment, volunteers had mild, transient flu-like symptoms and markedly increased serum levels of tumor necrosis factor and its soluble receptors, interleukin-6, cortisol, serum amyloid A, and C-reactive protein. Triglyceride (TG), VLDL-TG, and nonesterified fatty acid increased (peak at 3-4 h), then TG declined (nadir at 9 h), and then cholesterol, LDL cholesterol, apolipoprotein B (apoB), and phospholipid declined (nadirs at 12-24 h). HDL cholesterol and apoA-I levels were not affected, but half of the decrease in phospholipid was HDL phospholipid. Lipopolysaccharide binding protein (LBP) rose 3-fold (peak at 12 h), with smaller and later decreases in the activities of phospholipid transfer protein and cholesteryl ester transfer protein. In conclusion, a decline in LDL was rapidly induced in normal volunteers with a single iv dose of endotoxin. The selective loss of phospholipid from HDL may have been mediated by LBP and, after more intense or prolonged inflammation, could result in increased HDL clearance and reduced HDL levels.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.