Triglyceride-rich lipoproteins improve survival when given after endotoxin in rats.
BACKGROUND
Triglyceride-rich lipoproteins have been shown to bind bacterial endotoxin and inhibit its activity in vitro and to protect animals from death when administered before a lethal injection of endotoxin. We now demonstrate that triglyceride-rich lipoproteins can neutralize the toxic effects of endotoxin already in circulation.


METHODS
Rats were infused with a lethal dose of endotoxin, followed at various time intervals by an infusion of either mesenteric lymph containing nascent chylomicrons (1 gm chylomicron triglyceride/kg) or an equal volume of normal saline solution. Survival was measured at 48 hours. The experiment was then repeated, substituting the synthetic triglyceride-rich lipid emulsion (1 gm/kg) for chylomicrons. We also measured the clearance and tissue distribution of radioiodinated endotoxin in rats treated subsequently with chylomicrons or saline solution.


RESULTS
Chylomicron infusions significantly improved survival when given up to 30 minutes after a lethal dose of endotoxin (p < 0.05). Chylomicrons accelerated endotoxin clearance from the blood and increased endotoxin uptake by the liver. The synthetic triglyceride-rich lipid emulsion significantly improved survival when given up to 15 minutes after a lethal dose of endotoxin (p < 0.05).


CONCLUSIONS
Triglyceride-rich lipoproteins and synthetic triglyceride-rich lipid emulsions significantly improve survival of rats when given after a lethal dose of endotoxin. Lipoprotein treatment accelerates endotoxin clearance to the liver, which may account for the observed protection. These data suggest a possible therapeutic role for triglyceride-rich lipoproteins or synthetic lipid emulsions in the treatment of the endotoxemia of gram-negative sepsis.
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Department of Surgery, University of California, San Francisco.
Grunfeld
C
C
Kumwenda
Z
Z
Calhoun
M C
MC
Kane
J P
JP
Feingold
K R
KR
Rapp
J H
JH
D000818:Animals; D002914:Chylomicrons / Q000627:therapeutic use*; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D007928:Lethal Dose 50; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014115:Toxemia / Q000188:drug therapy* / Q000378:metabolism; D014280:Triglycerides / Q000627:therapeutic use*
D002914:Chylomicrons; D004731:Endotoxins; D005217:Fat Emulsions, Intravenous; D007457:Iodine Radioisotopes; D014280:Triglycerides