EFFECTS OF CHENODEOXYCHOLIC AND URSODEOXYCHOLIC ACIDS ON INTERFERON-GAMMA PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS

Ursodeoxycholic acid (UDCA) administration can obtain marked improveme nt of primary biliary cirrhosis (PBC). Recently, UDCA has been demonst rated to have a direct effect on immunological reactions in patients w ith PBC in that the aberrant expression of major histocompatibility co mplex (MHC) class I molecules was markedly reduced after UDCA treatmen t. To understand the immunological effect of UDCA, we analyzed interfe ron (IFN)-gamma production in peripheral blood mononuclear cells (PBMC s) from 29 patients with PBC treated with UDCA (group 1), 19 patients with PBC who were not treated with UDCA (group 2), 11 healthy subjects (group 3), and 12 patients with chronic viral hepatitis (group 4). IF N-gamma production was investigated because the excess production of t his cytokine is associated with the aberrant expression of MHC molecul es. Whereas IFN-gamma production in the patients in group 2 was signif icantly increased, the level of production in group 1 was similar to t hat in the control groups (groups 3 and 4). There was significant impr ovement in IFN-gamma production in 6 patients with PBC after UDCA trea tment. The effect of UDCA and chenodeoxycholic acid (CDCA) on IFN-gamm a production in PBMCs from 12 normal subjects was also analyzed. IFN-g amma was produced dose-dependently according to concentrations of CDCA ranging from 0.1 to 10 mu M, but the increase in production was marke dly suppressed by the addition of UDCA. We conclude that low doses of CDCA enhance IFN-gamma production and may therefore lead to the aberra nt hepatic expression of MHC molecules, and that the increase in IFN-g amma production is suppressed by UDCA.