Intragastric administration of ursodeoxycholic acid suppresses immunoglobulin secretion by lymphocytes from liver, but not from peripheral blood, spleen or Peyer’s patches in mice

Abstract

Ursodeoxycholic acid (UDCA) has been recognized as a therapeutic drug for primary biliary cirrhosis (PBC) and chronic viral hepatitis. As one of the mechanisms by which UDCA improves liver function tests in those patients, its immunomodulatory effect is currently considered important. Although the suppressive effects of UDCA on some cytokine productions, T-cell mediated cytotoxicity and immunoglobulin production were observed from in vitro studies, the immunomodulation in vivo by UDCA remains unclear. In the present study, we investigated the effect of UDCA administration on the number of immunoglobulin secreting cells in liver, peripheral blood, spleen and Peyer’s patches in mice using the enzyme linked immunospot assay and assessed whether the UDCA-mediated immunomodulation is liver-specific. It was demonstrated that intragastric administration of UDCA reduced immunoglobulin secretion by lymphocytes from liver, but not from peripheral blood, spleen, or Peyer’s patches. However, immunoglobulin production of those lymphocytes cultured in the presence of UDCA was suppressed, irrespective of their distribution sites, in a UDCA dose-dependent manner. When the concentrations of UDCA in portal and peripheral blood were measured using high performance liquid chromatography, UDCA was detectable in the portal blood in UDCA-treated mice, but not in peripheral blood, suggesting that the concentrations of UDCA in the environment surrounding lymphocytes may be an important factor for the modulation of lymphocyte functions.