Suppression of renal disease and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE) by chenodeoxycholic acid.

Published

Journal Article

The objective of this study was to examine the effects of ursodeoxycholic (UDCA) and chenodeoxycholic acid (CDCA) on autoimmune disease in the NZB x NZW F1 (B/W) mouse model of systemic lupus erythematosus (SLE). The development of murine lupus was assessed in female B/W mice given UDCA or CDCA. At 6 week intervals mice were examined for weight change, albuminuria, anti-DNA antibody and total IgG levels. Morbidity and mortality were assessed daily. UDCA- and CDCA-treated mice were examined at 24 weeks of age for serum cytokines, lymphocyte phenotype, and in vitro cytokine production after immunization with DNP-KLH. Liver and kidneys were examined histopathologically. The administration of UDCA and CDCA was tolerated without side effects. Weight gain in UDCA- or CDCA-treated and control mice was identical through 24 weeks of age. CDCA, but not UDCA, suppressed the development of renal disease. CDCA-treated B/W mice also had improved survival compared to UDCA-treated or control B/W mice. There were no significant effects of CDCA on anti-DNA antibodies, serum total IgG, or other immunologic parameters. CDCA-treated mice had lower serum IFN-gamma concentrations compared to control and UDCA-treated mice. The bile acid, CDCA, significantly inhibited the development of renal disease and modestly prolonged lifespan in the female B/W mouse model of SLE. Suppression of glomerulonephritis was associated with lower serum IFNgamma concentrations. Further investigation is needed to verify potential mechanisms of action, but these findings suggest that bile acids may alter the development or progression of autoimmunity.

Full Text

Duke Authors

Cited Authors

  • Suwannaroj, S; Lagoo, A; McMurray, RW

Published Date

  • 2001

Published In

Volume / Issue

  • 10 / 8

Start / End Page

  • 562 - 567

PubMed ID

  • 11530998

Pubmed Central ID

  • 11530998

International Standard Serial Number (ISSN)

  • 0961-2033

Digital Object Identifier (DOI)

  • 10.1191/096120301701549697

Language

  • eng

Conference Location

  • England