Suwannaroj S, Lagoo A, McMurray R W
Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Lupus. 2001;10(8):562-7. doi: 10.1191/096120301701549697.
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.
本研究的目的是在系统性红斑狼疮（SLE）的NZB×NZW F1（B/W）小鼠模型中，研究熊去氧胆酸（UDCA）和鹅去氧胆酸（CDCA）对自身免疫性疾病的影响。在给予UDCA或CDCA的雌性B/W小鼠中评估小鼠狼疮的发展情况。每隔6周检查小鼠的体重变化、蛋白尿、抗DNA抗体和总IgG水平。每天评估发病率和死亡率。在24周龄时，对接受UDCA和CDCA治疗的小鼠进行血清细胞因子、淋巴细胞表型以及用二硝基苯-钥孔戚血蓝蛋白（DNP-KLH）免疫后体外细胞因子产生情况的检查。对肝脏和肾脏进行组织病理学检查。UDCA和CDCA的给药耐受性良好，无副作用。在24周龄前，接受UDCA或CDCA治疗的小鼠与对照小鼠的体重增加情况相同。CDCA可抑制肾脏疾病的发展，但UDCA无此作用。与接受UDCA治疗或对照的B/W小鼠相比，接受CDCA治疗的B/W小鼠的存活率也有所提高。CDCA对抗DNA抗体、血清总IgG或其他免疫参数无显著影响。与对照小鼠和接受UDCA治疗的小鼠相比，接受CDCA治疗的小鼠血清干扰素-γ（IFN-γ）浓度较低。胆汁酸CDCA可显著抑制雌性B/W小鼠SLE模型中肾脏疾病的发展，并适度延长寿命。肾小球肾炎的抑制与血清IFN-γ浓度降低有关。需要进一步研究以验证潜在的作用机制，但这些发现表明胆汁酸可能会改变自身免疫的发展或进程。
