Faculty Collaboration Database

Chronic Staphylococcal enterotoxin B and lipopolysaccharide induce a bimodal pattern of hepatic dysfunction and injury. Crit Care Med 2003 Apr;31(4):1154-9

Date

04/19/2003

Pubmed ID

12682487

DOI

10.1097/01.CCM.0000060004.85054.F2

Scopus ID

2-s2.0-0037390799 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

OBJECTIVE: To determine the effect of chronic exposure to endotoxin (lipopolysaccharide) and Staphylococcal enterotoxin B on hepatic injury and function.

DESIGN: Prospective, controlled trial.

SETTING: Research laboratory in a university hospital.

SUBJECTS: Male Sprague-Dawley rats weighing 325-350 g with chronic vascular and bile catheters.

INTERVENTIONS: Chronically catheterized rats were treated daily with saline, 50 microg/kg Staphylococcal enterotoxin B alone, 1000 microg/kg lipopolysaccharide alone, 1000 microg/kg lipopolysaccharide with 50 microg/kg Staphylococcal enterotoxin B, or 100 microg/kg lipopolysaccharide with 50 microg/kg Staphylococcal enterotoxin B for 10 days. Serum and biliary measures of hepatic injury and dysfunction were measured before and then 6 hrs and 1, 2, 3, 7, and 10 days after the start of treatment. The animals were killed at 10 days and the livers examined histologically.

MEASUREMENTS AND MAIN RESULTS: Mean rates of bile flow, biliary indocyanine green excretion, and bile acid flux were significantly decreased immediately after treatment (6 hr, 1 and 2 days) and then at 10 days. Increases in biliary and serum gamma-glutamyltransferase and serum bile acids also occurred in a similar bimodal pattern. Animals treated with lipopolysaccharide or Staphylococcal enterotoxin B alone became tolerant and did not develop the bimodal pattern of hepatic dysfunction. Histologic examination of the liver at 10 days revealed periportal inflammation and fibrosis.

CONCLUSIONS: The combination of lipopolysaccharide and Staphylococcal enterotoxin B leads to late liver injury, whereas either toxin alone does not. These data may explain the frequent development of liver dysfunction in patients exposed to multiple bacterial toxins such as in sepsis, multiple-system organ failure, and other diseases with altered intestinal permeability.

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

Alanine Transaminase
Animals
Bile
Bile Acids and Salts
Enterotoxins
Escherichia coli
Indocyanine Green
Infusions, Intravenous
Interferon-gamma
Lipopolysaccharides
Liver
Liver Diseases
Liver Function Tests
Male
Multiple Organ Failure
Rats
Rats, Sprague-Dawley
Sepsis
Staphylococcus aureus
Superantigens
Tumor Necrosis Factor-alpha
gamma-Glutamyltransferase