J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M200440-JLR200 on May 16, 2003

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Journal of Lipid Research, Vol. 44, 1489-1498, August 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers

Lisa C. Hudgins1,*,{dagger}, Thomas S. Parker*,{dagger}, Daniel M. Levine*,{dagger}, Bruce R. Gordon*,{dagger}, Stuart D. Saal*,{dagger}, Xian-cheng Jiang§, Cindy E. Seidman*, Jolanta D. Tremaroli*, Julie Lai* and Albert L. Rubin{dagger},*

* The Rockefeller University, 1230 York Avenue, New York, NY 10021
{dagger} The Rogosin Institute, 505 East 70th Street, New York, NY 10021
§ SUNY Downstate Health Sciences Center, 450 Clarkson Avenue, Brooklyn, NY 11203

1 To whom correspondence should be addressed. e-mail: hudgins{at}mail.rockefeller.edu

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.

Supplementary key words lipopolysaccharide • sepsis • phospholipid • cholesterol • triglyceride • lipopolysaccharide binding protein • phospholipid transfer protein • cholesteryl ester transfer protein • high density lipoprotein • low density lipoprotein


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