title: Portal hypertension enhances endotoxin-induced intercellular adhesion molecule 1 up-regulation in the rat.
abstract: 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.
authors.affiliation: Department of Physiology, Louisiana State University Medical Center, Shreveport, USA.
authors.forename: J
authors.initials: J
authors.lastname: Panés
authors.forename: M A
authors.initials: MA
authors.lastname: Perry
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
authors.forename: V R
authors.initials: VR
authors.lastname: Muzykantov
authors.forename: D L
authors.initials: DL
authors.lastname: Carden
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
mesh_terms: 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
chemical_list: D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1