PORTAL-HYPERTENSION ENHANCES ENDOTOXIN-INDUCED INTERCELLULAR-ADHESIONMOLECULE-1 UP-REGULATION IN THE RAT

Background & Aims: Liver disease or portosystemic shunting enhances th e sensitivity to endotoxin, The aim of this study was to investigate w hether intercellular adhesion molecule 1 (ICAM-1) expression in respon se to endotoxin may be dysregulated in an animal model of portal hyper tension. Methods: Portal hypertension was induced by partial portal ve in ligation, Sham-operated animals served as controls, ICAM-1 expressi on was measured using radiolabeled antibodies under baseline condition s or 5 hours after treatment with either endotoxin or recombinant tumo r necrosis factor (TNF), Immunoreactive plasma TNF was also measured, Results: Under baseline conditions, ICAM-1 expression in all organs st udied was similar in portal-hypertensive and sham-operated rats. ICAM- 1 up-regulation after a high dose of endotoxin (5 mg/kg) was similar i n both groups of animals, However, portal-hypertensive animals showed a significantly higher ICAM-1 expression in response to low doses of e ndotoxin (0.1-10 mu g/kg). The response to a low (but not a high) dose of recombinant TNF was also significantly enhanced in portal-hyperten sive animals. In addition, portal-hypertensive rats had higher plasma TNF levels after treatment with endotoxin or recombinant TNF, Conclusi ons: Portal hypertension induces an exaggerated ICAM-1 up-regulation i n response to endotoxin, which is related to an increased production a nd decreased clearance of the cytokine.