Effects of chenodeoxycholic and ursodeoxycholic acids on interferon-gamma production by peripheral blood mononuclear cells from patients with primary biliary cirrhosis

Abstract

Ursodeoxycholic acid (UDCA) administration can obtain marked improvement of primary biliary cirrhosis (PBC). Recently, UDCA has been demonstrated to have a direct effect on immunological reactions in patients with PBC in that the aberrant expression of major histocompatibility complex (MHC) class I molecules was markedly reduced after UDCA treatment. To understand the immunological effect of UDCA, we analyzed interferon (IFN)-gamma production in peripheral blood mononuclear cells (PBMCs) 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). IFN-gamma production was investigated because the excess production of this cytokine is associated with the aberrant expression of MHC molecules. Whereas IFN-gamma production in the patients in group 2 was significantly increased, the level of production in group 1 was similar to that in the control groups (groups 3 and 4). There was significant improvement in IFN-gamma production in 6 patients with PBC after UDCA treatment. The effect of UDCA and chenodeoxycholic acid (CDCA) on IFN-gamma production in PBMCs from 12 normal subjects was also analyzed. IFN-gamma was produced dose-dependently according to concentrations of CDCA ranging from 0.1 to 10 microM, but the increase in production was markedly suppressed by the addition of UDCA. We conclude that low doses of CDCA enhance IFN-gamma production and may therefore lead to the aberrant hepatic expression of MHC molecules, and that the increase in IFN-gamma production is suppressed by UDCA.