Faculty Collaboration Database

Staphylococcal enterotoxin B potentiates LPS-induced hepatic dysfunction in chronically catheterized rats. Am J Physiol Gastrointest Liver Physiol 2001 May;280(5):G866-72

Date

04/09/2001

Pubmed ID

11292594

DOI

10.1152/ajpgi.2001.280.5.G866

Scopus ID

2-s2.0-0035036687 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Most models of liver dysfunction in sepsis use endotoxin (lipopolysaccharide; LPS) to induce a pathophysiological response. In our study published in this issue (Beno DWA, Uhing MR, Goto M, Chen Y, Jiyamapa-Serna VA, and Kimura RE. Am J Physiol Gastrointest Liver Physiol 280: G858-G865, 2001), the adverse effect of LPS on hepatic function in vivo was only significant at relatively high LPS doses despite high tumor necrosis factor-alpha concentrations. However, many patients with sepsis are exposed to multiple bacterial toxins that may augment the immune response, resulting in increased hepatic dysfunction. We have developed a model of polymicrobial sepsis by parentally administering a combination of staphylococcal enterotoxin B (SEB) and LPS. Using this model, we demonstrate that SEB (50 microg/kg) potentiates the effect of LPS-induced hepatic dysfunction as measured by decreased rates of biliary indocyanine green clearance and bile flow. These increases were most pronounced with doses of 10 and 100 microg/kg LPS, doses that by themselves do not induce hepatic dysfunction. This may explain the seemingly increased incidence and severity of liver dysfunction in sepsis, and it suggests that the exclusive use of LPS for replicating septic shock may not be relevant for studies of hepatic dysfunction.

Author List

Beno DW, Uhing MR, Goto M, Chen Y, Jiyamapa-Serna VA, 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
Antigens, Bacterial
Bile
Catheters, Indwelling
Drug Synergism
Enterotoxins
Escherichia coli
Indocyanine Green
Interferon-gamma
Kinetics
Lipopolysaccharides
Liver
Male
Rats
Rats, Sprague-Dawley
Recombinant Proteins
Staphylococcus
Time Factors
Tumor Necrosis Factor-alpha