title: Chronic Staphylococcal enterotoxin B and lipopolysaccharide induce a bimodal pattern of hepatic dysfunction and injury.
abstract: OBJECTIVE
  To determine the effect of chronic exposure to endotoxin (lipopolysaccharide) and Staphylococcal enterotoxin B on hepatic injury and function.
  
  
  METHODS
  Prospective, controlled trial.
  
  
  METHODS
  Research laboratory in a university hospital.
  
  
  METHODS
  Male Sprague-Dawley rats weighing 325-350 g with chronic vascular and bile catheters.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Section of Neonatology, Department of Pediatrics, Rush Children's Hospital, Rush Presbyterian St. Luke's Medical Center, 1653 W. Congress Pkwy, Chicago, IL 60612, USA. dbeno@rush.edu
authors.forename: David W A
authors.initials: DW
authors.lastname: Beno
authors.forename: Michael R
authors.initials: MR
authors.lastname: Uhing
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Goto
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Vanida A
authors.initials: VA
authors.lastname: Jiyamapa-Serna
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kimura
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001646:Bile / Q000502:physiology; D001647:Bile Acids and Salts / Q000097:blood; D004768:Enterotoxins / Q000008:administration & dosage*; D004926:Escherichia coli; D007208:Indocyanine Green; D007262:Infusions, Intravenous; D007371:Interferon-gamma / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008099:Liver / Q000503:physiopathology*; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D009102:Multiple Organ Failure / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000503:physiopathology*; D013211:Staphylococcus aureus; D018089:Superantigens / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D005723:gamma-Glutamyltransferase / Q000032:analysis
chemical_list: D001647:Bile Acids and Salts; D004768:Enterotoxins; D008070:Lipopolysaccharides; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D007208:Indocyanine Green