A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers.
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.
Hudgins
Lisa C
LC
The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. hudgins@mail.rockefeller.edu
Parker
Thomas S
TS
Levine
Daniel M
DM
Gordon
Bruce R
BR
Saal
Stuart D
SD
Jiang
Xian-Cheng
XC
Seidman
Cindy E
CE
Tremaroli
Jolanta D
JD
Lai
Julie
J
Rubin
Albert L
AL
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002352:Carrier Proteins / Q000097:blood*; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007249:Inflammation / Q000097:blood; D007275:Injections, Intravenous; D008074:Lipoproteins / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D000685:Serum Amyloid A Protein / Q000032:analysis; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; D004731:Endotoxins; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D000685:Serum Amyloid A Protein; D014280:Triglycerides; C030363:lipid transfer protein; C030106:very low density lipoprotein triglyceride; D002097:C-Reactive Protein; D006854:Hydrocortisone