Splanchnic Th2 and Th1 Cytokine Redistribution in Microsurgical Cholestatic Rats

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. Material and Methods We measured serum levels of hepatobiliary injury markers and the acute phase proteins, alpha-1-major acid protein (α 1 -MAP) and alpha-1-acid glycoprotein (α 1 -GPA) in rats 6 wk after microsurgical extrahepatic cholestasis. We also assayed Th 1 (TNF-α and IL-1β) 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 1 - MAP, α 1 -GPA, and LDH ( P P P P P Conclusion 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.