Portal hypertension enhances endotoxin-induced intercellular adhesion molecule 1 up-regulation in the rat.
OBJECTIVE
Liver disease or portosystemic shunting enhances th e sensitivity to endotoxin. The aim of this study was to investigate whether intercellular adhesion molecule 1 (ICAM-1) expression in response to endotoxin may be dysregulated in an animal model of portal hypertension.


METHODS
Portal hypertension was induced by partial portal vein ligation. Sham-operated animals served as controls. ICAM-1 expression was measured using radiolabeled antibodies under baseline conditions or 5 hours after treatment with either endotoxin or recombinant tumor necrosis factor (TNF). Immunoreactive plasma TNF was also measured.


RESULTS
Under baseline conditions, ICAM-1 expression in all organs studied was similar in portal-hypertensive and sham-operated rats. ICAM-1 up-regulation after a high dose of endotoxin (5 mg/kg) was similar in both groups of animals. However, portal-hypertensive animals showed a significantly higher ICAM-1 expression in response to low doses of endotoxin (0.1-10 microgram/kg). The response to a low (but not a high) dose of recombinant TNF was also significantly enhanced in portal-hypertensive animals. In addition, portal-hypertensive rats had higher plasma TNF levels after treatment with endotoxin or recombinant TNF.


CONCLUSIONS
Portal hypertension induces an exaggerated ICAM-1 up-regulation in response to endotoxin, which is related to an increased production and decreased clearance of the cytokine.
Panés
J
J
Department of Physiology, Louisiana State University Medical Center, Shreveport, USA.
Perry
M A
MA
Anderson
D C
DC
Muzykantov
V R
VR
Carden
D L
DL
Miyasaka
M
M
Granger
D N
DN
D000704:Analysis of Variance; D000818:Animals; D004064:Digestive System / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology*; D006975:Hypertension, Portal / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1