title: Splanchnic Th(2) and Th(1) cytokine redistribution in microsurgical cholestatic rats.
abstract: BACKGROUND
  Long-term extrahepatic cholestasis in the rat induces ductular proliferation and fibrosis in the liver, portal hypertension, splenomegaly, portosystemic collateral circulation, and ascites. These splanchnic alterations could have an inflammatory pathophysiology.
  
  
  METHODS
  We measured serum levels of hepatobiliary injury markers and the acute phase proteins, alpha-1-major acid protein (alpha(1)-MAP) and alpha-1-acid glycoprotein (alpha(1)-GPA) in rats 6 wk after microsurgical extrahepatic cholestasis. We also assayed Th(1) (TNF-alpha and IL-1beta) and Th(2) (IL-4 and IL-10) cytokine levels in the liver, ileum, spleen, and mesenteric lymph complex by enzyme-linked immunosorbent assay (ELISA) techniques. Liver fibrosis was measured by Sirius red stain and by using an image system computer-assisted method and mast cell liver infiltration by Giemsa stain.
  
  
  RESULTS
  The cholestatic rats showed an increase (P<0.001) in serum levels of bile acids, total and direct bilirubin, AST, ALT, AST/ALT index, gamma-GT, alkaline phosphatase, alpha(1)- MAP, alpha(1)-GPA, and LDH (P<0.05) in relation to sham-operated rats. TNF-alpha, IL-1beta, IL-4, and IL-10 increased in the ileum (P<0.01) and mesenteric lymph complex (P<0.001), and decreased in the liver (P<0.001). A marked bile proliferation associated with fibrosis (P<0.001) and mast cell infiltration was also shown in the liver of cholestatic rats.
  
  
  CONCLUSIONS
  The splanchnic redistribution of cytokines, with an increase of Th(1) and Th(2) production in the small bowel and in the mesenteric lymph complex, supports the key role of inflammatory mechanisms in rats with secondary biliary fibrosis.
authors.affiliation: Plastic Surgery Unit, Getafe University Hospital, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: García-Dominguez
authors.forename: María-Angeles
authors.initials: MA
authors.lastname: Aller
authors.forename: Cruz
authors.initials: C
authors.lastname: García
authors.forename: Felipe
authors.initials: F
authors.lastname: de Vicente
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Corcuera
authors.forename: Fernando
authors.initials: F
authors.lastname: Gómez-Aguado
authors.forename: María José
authors.initials: MJ
authors.lastname: Alonso
authors.forename: Elena
authors.initials: E
authors.lastname: Vara
authors.forename: Jaime
authors.initials: J
authors.lastname: Arias
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002779:Cholestasis / Q000601:surgery*; D003097:Collateral Circulation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D007082:Ileum / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008642:Mesenteric Veins / Q000503:physiopathology; D008866:Microsurgery / Q000379:methods; D009929:Organ Size; D011169:Portal Vein / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4