Staphylococcal enterotoxin B potentiates LPS-induced hepatic dysfunction in chronically catheterized rats.
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.
Beno
D W
DW
Section of Neonatology, Department of Pediatrics, Rush Children's Hospital, Rush Presbyterian St. Luke's Medical Center, 1653 W. Congress, Chicago, IL 60612.
Uhing
M R
MR
Goto
M
M
Chen
Y
Y
Jiyamapa-Serna
V A
VA
Kimura
R E
RE
D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D002408:Catheters, Indwelling; D004357:Drug Synergism; D004768:Enterotoxins / Q000633:toxicity*; D004926:Escherichia coli; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013210:Staphylococcus; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D000942:Antigens, Bacterial; D004768:Enterotoxins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D007208:Indocyanine Green