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Differential induction of hepatic dysfunction after intraportal and intravenous challenge with endotoxin and Staphylococcal enterotoxin B. Shock 2003 Apr;19(4):352-7

Date

04/12/2003

Pubmed ID

12688547

DOI

10.1097/00024382-200304000-00010

Scopus ID

2-s2.0-0038113413   9 Citations

Abstract

We have previously shown that systemic infusion of the bacterial toxins Staphylococcal enterotoxin B (SEB) and endotoxin (LPS) induces hepatic dysfunction as measured by decreased biliary indocyanine green (ICG) excretion. In this study, we compare the effects of these bacterial toxins after infusion into the portal and systemic circulation and directly measure biliary bile acid excretion as a measure of cholestasis. We hypothesized that bacterial toxins infused into the portal vein would induce greater hepatic dysfunction than toxins infused into the systemic circulation. Using a chronically catheterized rat model, biliary bile acid excretion was directly measured after infusion of LPS at 10 and 100 microg/kg with and without 50 microg/kg SEB into the portal vein (IPV) or inferior vena cava (IV) at baseline, and at 6 and 24 h. We found that when LPS was infused alone, only IPV administration caused a significant decrease in bile acid excretion at 6 h. There was no change in bile acid excretion after IV administration of LPS. In contrast, when the combination of LPS and SEB was infused, both IV and IPV administration significantly decreased bile acid excretion at 6 and 24 h. At 6 h post-LPS and -SEB administration, the decrease in bile acid excretion was significantly greater after IPV than IV administration. There was no site-specific difference in IFN-gamma release after infusion of toxins. However, peak TNFalpha release was decreased in IPV-infused rats [10 microg/kg (P < 0.05) or 100 microg/kg (P = ns) LPS with SEB] compared with the same doses in IV-infused rats. These data question the role of systemic TNF-alpha and IFN-gamma in regulating hepatic dysfunction and suggest a differential functional response of the liver to systemic and gut-derived septic events. This study also further explains the frequent development of liver dysfunction in patients with sepsis, multisystem organ failure, and other diseases with altered intestinal permeability.

Author List

Beno DW, Uhing MR, Jiyamapa-Serna VA, Goto M, Chen Y, Vasan A, Deriy LV, Kimura RE

Author

Michael R. Uhing MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bile
Bile Acids and Salts
Chemical and Drug Induced Liver Injury
Endotoxins
Enterotoxins
Injections, Intravenous
Male
Portal Vein
Rats
Rats, Sprague-Dawley
Vena Cava, Inferior