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

  • Liver, Pancreas, and Biliary Tract
  • Published:
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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)-γ 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-γ production was investigated because the excess production of this cytokine is associated with the aberrant expression of MHC molecules. Whereas IFN-γ 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-γ production in 6 patients with PBC after UDCA treatment. The effect of UDCA and chenodeoxycholic acid (CDCA) on IFN-γ production in PBMCs from 12 normal subjects was also analyzed. IFN-γ was produced dose-dependently according to concentrations of CDCA ranging from 0.1 to 10 μM, but the increase in production was markedly suppressed by the addition of UDCA. We conclude that low doses of CDCA enhance IFN-γ production and may therefore lead to the aberrant hepatic expression of MHC molecules, and that the increase in IFN-γ production is suppressed by UDCA.

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References

  1. Kaplan MM. Primary biliary cirrhosis. N Engl J Med 1987;316: 521–528.

    CAS  PubMed  Google Scholar 

  2. Ballardini G, Mirakian R, Bianchi FB, et al. Aberrant expression of HLA-DR antigens on bile duct epithelium in primary biliary cirrhosis: Relevance to pathogenesis. Lancet 1984;II:1009–1013.

    Google Scholar 

  3. Calmus Y, Gane P, Rouger P, Poupon R. Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: Effect of ursodeoxycholic acid. Hepatology 1990;11:12–15.

    CAS  PubMed  Google Scholar 

  4. Terasaki S, Nakanuma Y, Ogino H, et al. Hepatocellular and biliary expression of HLA antigens in primary biliary cirrhosis before and after ursodeoxycholic acid therapy. Am J Gastroenterol 1991;86:1194–1199.

    CAS  PubMed  Google Scholar 

  5. Poupon R, Chrétien Y, Poupon RE, et al. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet 1987;II:834–836.

    Google Scholar 

  6. Leuschner U, Fischer H, Kurtz W, et al. Ursodeoxycholic acid in primary biliary cirrhosis: Results of a controlled double-blind trial. Gastroenterology 1989;97:1268–1274.

    CAS  PubMed  Google Scholar 

  7. Poupon RE, Balkau B, Eschwége E, Poupon R, and the UDCA-PBC study group. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. N Engl J Med 1991;324:1548–1554.

    CAS  PubMed  Google Scholar 

  8. Basham TY, Mergan TC. Recombinant interferon-γ increases HLA-DR synthesis and expression. J Immunol 1983;130:1492–1494.

    CAS  PubMed  Google Scholar 

  9. Heron I, Hokland M, Berg K. Enhanced expression of β2-microglobulin and HLA antigens on human lymphoid cells by interferon. Proc Natl Acad Sci USA 1978;75:6215–6219.

    CAS  PubMed  Google Scholar 

  10. James SP, Elson CO, Waggoner JG, et al. Deficiency of the autologous mixed lymphocyte reaction in patients with primary biliary cirrhosis. J Clin Invest 1980;66:1305–1310.

    CAS  PubMed  Google Scholar 

  11. Scheuer PJ. Primary biliary cirrhosis. Proc Roy Soc Med 1967; 60:1257–1267.

    CAS  PubMed  Google Scholar 

  12. Wakasugi N. Interferon-γ. Clin Immunol 1987;19 [Suppl 12]: 178–186.

    Google Scholar 

  13. Podda M, Ghezzi C, Bettezzani PM, et al. Ursodeoxycholic acid for chronic liver disease. J Clin Gastroenterol 1988;10 [Suppl 2]: s25-s31.

    PubMed  Google Scholar 

  14. Batta AK, Arora R, Salen G, et al. Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: Effect of ursodeoxycholic acid treatment. J Lipid Res 1989;30:1953–1962.

    CAS  PubMed  Google Scholar 

  15. Marteau P, Chazouilleres O, Myara A, et al. Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acid in man. Hepatology 1990;12:1206–1208.

    CAS  PubMed  Google Scholar 

  16. de Caestecker JS, Jazrawi RP, Petroni ML, Northfield TC. Ursodeoxycholic acid in chronic liver disease. Gut 1991;32: 1061–1065.

    PubMed  Google Scholar 

  17. Lacaille F, Paradis K. The immunosuppressive effect of ursodeoxycholic acid: A comparative in vitro study on human peripheral blood mononuclear cells. Hepatology 1993;18:165.

    Article  CAS  PubMed  Google Scholar 

  18. Calmus Y, Weill B, Ozier Y, et al. Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse. Gastroenterology 1992;103:617.

    CAS  PubMed  Google Scholar 

  19. Calmus Y, Guechot J, Podevin P, et al. Different effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6, and tumor necrosis factor-α production by monocytes. Hepatology 1992;16:719.

    CAS  PubMed  Google Scholar 

  20. Innes GK, Nagafuchi Y, Fuller BJ, Hobbs KEF. Increased expression of major histocompatibility antigens in the liver as a result of cholestasis. Transplantation 1988;45:749–752.

    CAS  PubMed  Google Scholar 

  21. Arvieux C, Calmus Y, Gane P, et al. Quantitation and modulation of major histocompatibility complex (MHC) expression: The effect of cholestasis and immunosuppressive drugs. J Hepatol 1990;11:s2.

    Article  Google Scholar 

  22. Calmus Y, Poupon R. Ursodeoxycholic acid (UDCA) in the treatment of chronic cholestatic diseases. Biochimie 1991;73: 1335–1338.

    Article  CAS  PubMed  Google Scholar 

  23. Hirao F, Tanaka H, Makino I. Chenodeoxycholic acid-dependent induction of major histocompatibility complex class I mRNA expression in a human hepatoma cell line. Biochem Biophys Res Commun 1993;195:1408.

    Google Scholar 

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Saeki, R., Ogino, H., Kaneko, S. et al. Effects of chenodeoxycholic and ursodeoxycholic acids on interferon-γ production by peripheral blood mononuclear cells from patients with primary biliary cirrhosis. J Gastroenterol 30, 739–744 (1995). https://doi.org/10.1007/BF02349640

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  • DOI: https://doi.org/10.1007/BF02349640

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