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Abstract
Background and aims Teriflunomide sodium (CK8) is the sodium salt of the metabolites of the leflunomide. Leflunomide has been approved for the treatment of lupus nephritis by CFDA.The aim of the study was to evaluate the therapeutic effect of CK8 on the course of disease in SLE-prone MRL/lpr mice, compared with leflunomide and glucocorticoid.
Methods Ten to eleven-weeks-old female mice displaying clinical symptoms of SLE were given CK8 (20 mg/kg, 30 mg/kg, 40 mg/kg) gavage once a day for 8 weeks. Control mice received gavage of leflunomide (30 mg/kg) , Prednisone Acetate (2 mg/kg) or vehicle. Survival, proteinuria , lupus like skin lesion, lymphoid organ ,level of anti-dsDNA antibodies and IL-17 in serum, double negative(DN) T cells and regulatory T cell were analysed.
Results The results show that after treatment 8 weeks , 3 of 12 mice in vehicle control group led to death because of severe SLE, but mice all survived in CK8 30 mg/kg group. CK8 can effectively improve the skin lesions, swollen of lymph nodes and spleen and other symptoms of lupus, reduce proteinuria (Figure 1), the level of serum anti-dsDNA antibody(Figure 2) and IL-17(Figure 3), and a significant dose-response relationship. Further study found that treatment with CK8 can significantly reduce glomerular nephritis and interstitial nephritis lesions in MRL/lpr mouse ,but leflunomide without obvious improvement . CK8 can significantly decrease proportion of the DN T cells, increase proportion of regulatory T cells.
Conclusions The results suggest that the CK8 can effectively control progress of spontaneous lupus of MRL/lpr mouse, improve the symptoms and signs.