Suppression of renal disease and mortality in the female NZB x NZW F-1 mouse model of systemic lupus erythematosus (SLE) by chenodeoxycholic acid

The objective of this study was to examine the effects of ursodeoxycholic ( UDCA) and chenodeoxycholic acid (CDCA) on autoimmune disease in the NZB X N ZW F-1 (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, albuminu ria, anti-DNA antibody and total IgG levels. Morbidity and mortality were a ssessed daily. UDCA- and CDCA-treated mice were examined at 24 weeks of age for serum cytokines, lymphocyte phenotype, and in vitro cytokine productio n after immunization with DNP-KLH. Liver and kidneys were examined histopat hologically. The administration of UDCA and CDCA was tolerated without side effects. Wei ght 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 dise ase. CDCA-treated B/W mice also had improved survival compared to UDCA-trea ted or control B/W mice. There were no significant effects of CDCA on anti- DNA antibodies, scrum total IgG, or other immunologic parameters. CDCA-trea ted mice had lower serum IFN-gamma, concentrations compared to control and UDCA-treated mice. The bile acid, CDCA, significantly inhibited the development of renal disea se and modestly prolonged lifespan in the female B/W mouse model of SLE. Su ppression of glomerulonephritis was associated with lower serum IFN gamma c oncentrations. Further investigation is needed to verify potential mechanis ms of action, but these findings suggest that bile acids may alter the deve lopment or progression of autoimmunity.