Endotoxin tolerance in rats: influence on LPS-induced changes in excretory liver function.
OBJECTIVE
We investigated in a rat model of endotoxic shock whether endotoxin tolerance (ETT) prevents lipopolysaccharide (LPS) associated lethality and studied the initial function of liver response to LPS.


METHODS
Male Sprague-Dawley rats.


METHODS
ETT was induced by i.p. injection of LPS (Salmonella friedenau) intraperitoneally over 5 days. Rats (n = 6 each group) received 1 mg LPS/kg b. w. intravenously (Salmonella friedenau). The common bile duct was then canalized and bile was collected every 60 min for 6 h. 1 h after LPS-application liver biopsies were taken for determination of TNF-alpha by RT-PCR. Sham operated animals (n = 6 each group) were treated identically but without application of LPS.


RESULTS
All ETT animals survived the duration of the experiment whereas non-tolerant animals (NETT) died before the end of the experiment (5/6). NETT animals showed a continuous decrease in bile flow after 240 min. The amount of bile acids was significantly lower (ANOVA) in NETT animals than in sham operated controls or ETT-animals. Analysis of TNF-alpha mRNA expression in the liver revealed an upregulation 1 h after LPS application, which was significantly lower in LPS-tolerant animals.


CONCLUSIONS
Our results show that excretory liver failure and death subsequent to intravenous LPS application can be successfully counteracted by induction of ETT.
Domínguez Fernández
E
E
Department of General Surgery, Mannheim Medical School, University of Heidelberg, Theodor Kutzer-Ufer 1-3, DE-68167 Mannheim, Germany. emilio.dominguez@chir.ma.uni-heidelberg.de
Flohé
S
S
Siemers
F
F
Nau
M
M
Schade
F U
FU
D000818:Animals; D001646:Bile / Q000502:physiology; D001647:Bile Acids and Salts / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D004361:Drug Tolerance; D004731:Endotoxins / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012475:Salmonella / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001647:Bile Acids and Salts; D018076:DNA, Complementary; D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D012313:RNA