Does ursodeoxycholic acid mediate immunomodulatory and anti-inflammatory effects in patients with primary sclerosing cholangitis?

Background and objectives Therapy with ursodeoxycholic acid (UDCA) has been reported to be associated with improvements in abnormal serum biochemical liver tests in patients with primary sclerosing cholangitis (PSC). To evalu ate further the effects of UDCA on this disease, we evaluated immunological markers and indices of inflammation during a one-year, prospective, open-l abel trial of UDCA therapy in patients with PSC. Patients and methods Seventeen PSC patients were enrolled for one year of t reatment with UDCA 12-15 mg/kg/day. Serum biochemical variables, immunologi cal markers and indices of inflammation were compared before and at the end of therapy and 4 months after treatment had been withdrawn. Liver histolog y and immunohistochemistry for human leucocyte antigen (HLA) class I/II and intercellular adhesion molecule 1 (ICAM-1) expression were compared before and at the end of therapy. Results UDCA treatment was associated with significant improvements in seru m biochemical liver tests, immunoglobulin levels and blood coagulation fact ors. Tumour necrosis factor alpha (TNF-alpha) production after in vitro who le-blood phytohaemagglutinin (PHA) stimulation was increased, but unaltered by UDCA therapy. Baseline serum levels of interleukin-6 (IL-6) and soluble IL-2 receptor were normal, and serum IL-8 levels were increased, but none of these variables was significantly affected by UDCA therapy. Liver histol ogical stage/grade and HLA class I/II and ICAM-1 expression on biliary epit helial cells and hepatocytes were not markedly altered by UDCA therapy. Conclusions UDCA therapy in PSC patients was associated with a decrease in cholestasis, but no consistent improvement in hepatic inflammation, fibrosi s or histological stage of the disease. Immunomodulatory effects of UDCA in PSC do not appear to be HLA-restricted. (C) 1999 Lippincott Williams & Wil kins.