1. Splanchnic Th2 and Th1 Cytokine Redistribution in Microsurgical Cholestatic Rats
- Author
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Jaime Arias, Elena Vara, Maria-Teresa Corcuera, Cruz García, María José Alonso, Fernando Gómez-Aguado, Jose García-Domínguez, Felipe de Vicente, and Maria-Angeles Aller
- Subjects
Liver Cirrhosis ,Male ,Microsurgery ,Pathology ,medicine.medical_specialty ,Interleukin-1beta ,Collateral Circulation ,Blood Pressure ,Enzyme-Linked Immunosorbent Assay ,Extrahepatic Cholestasis ,chemistry.chemical_compound ,Mesenteric Veins ,Liver Function Tests ,Cholestasis ,Ileum ,Fibrosis ,Ascites ,medicine ,Animals ,Splanchnic Circulation ,Rats, Wistar ,Sirius Red ,medicine.diagnostic_test ,Portal Vein ,Tumor Necrosis Factor-alpha ,business.industry ,Body Weight ,Organ Size ,medicine.disease ,Interleukin-10 ,Rats ,Liver ,chemistry ,Surgery ,Interleukin-4 ,medicine.symptom ,Splanchnic ,Liver function tests ,business ,Spleen - Abstract
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.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.The cholestatic rats showed an increase (P0.001) 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 (P0.05) in relation to sham-operated rats. TNF-alpha, IL-1beta, IL-4, and IL-10 increased in the ileum (P0.01) and mesenteric lymph complex (P0.001), and decreased in the liver (P0.001). A marked bile proliferation associated with fibrosis (P0.001) and mast cell infiltration was also shown in the liver of cholestatic rats.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.
- Published
- 2010
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