Sophorae radix reduces autoimmune response in NZB/w F1 systemic lupus erythematosus mouse model

Abstract

The immunosuppressive effects of Sophorae radix (SR) make this plant an attractive agent for the treatment of autoimmune diseases. The effect of SR on systemic lupus erythematosus (SLE) in the New Zealand Black/White F₁ (NZB/w F₁) mouse model system was investigated. Three-month-old NZB/w F₁ mice were separated into two groups: one treated with SR (1% SR solution by oral administration, daily for 15 weeks) and one with water as a control. Experimental parameters include proteinuria, anti-dsDNA antibody titers, T-cell response and renal histopathological analysis. Results in the SR-treated group showed a significant reduction in proteinuria and anti-dsDNA antibodies either in serum or in glomerular capillaries, along with significant recovery from renal glomerular damage. The lymphocyte population was significantly increased in the SR-treated mice compared with the control group. In the T helper (Th)1/Th2 cytokine secretion profile, interferon-γ in splenocyte culture was significantly reduced in the SR-treated mice, while interleukin-4 secretion was not altered. These results strongly suggest SR therapy corrects the deviated Th1/Th2 balance, thereby alleviating SLE-like symptoms in the NZB/w F₁ mice. Therefore, SR may be useful in the clinical treatment of SLE. Lupus (2007) 16, 335—341.

Keywords

Sophorae radix SLE Th1 Th2

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References

Mosmann TR , Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996; 17: 138—146.

Rapoport MJ , Sharabi A. , Aharoni D. et al. Amelioration of SLE-like manifestations in (NZB×NZW)F1 mice following treatment with a peptide based on the complementarity determining region 1 of an autoantibody is associated with a down-regulation of apoptosis and of the pro-apoptotic factor JNK kinase. Clin Immunol 2005; 117: 262—270.

Singh RR , Hahn BH , Tsao BP et al. Evidence for multiple mechanisms of polyclonal T cell activation in murine lupus. J Clin Invest 1998; 102: 1841—1849.

Finck BK , Chan B. , Wofsy D. Interleukin 6 promotes murine lupus in NZB/NZW F1 mice. J Clin Invest 1994; 94: 585—591.

Yoshii H. , Yamamoto K. , Okudaira H. et al. Age-related differential mRNA expression of T cell cytokines in NZB/NZW F1 mice. Lupus 1995; 4: 213—216.

Santiago ML , Fossati L. , Jacquet C. et al. Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome. J Exp Med 1997; 185: 65—70.

Takahashi S. , Fossati L. , Iwamoto M. et al. Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice . J Clin Invest 1996; 97: 1597—1604.

Theofilopoulos AN , Kofler R. , Singer PA et al. Molecular genetics of murine lupus models. Adv Immunol 1989; 46: 61—109.

Howie JB , Helyer BJ The immunology and pathology of NZB mice. Adv Immunol 1968; 9: 215—266.

10.

Theofilopoulos AN , Dixon FJ Murine models of systemic lupus erythematosus . Adv Immunol 1985; 37: 269—390.

11.

Dueymes M. , Barrier J. , Besancenot JF et al. Relationship of interleukin-4 to isotypic distribution of anti-double-stranded DNA antibodies in systemic lupus erythematosus. Int Arch Allergy Immunol 1993; 101: 408—415.

12.

Hu ZL , Zhang JP , Qian DH et al. Effects of matrine on mouse splenocyte proliferation and release of interleukin-1 and -6 from peritoneal macrophages in vitro. Zhongguo Yao Li Xue Bao 1996; 17: 259—261.

13.

Chang MS , Xiao JG , Chiou GC Prevention of ocular inflammation by matrine, prednisolone, and cyclooxygenase and lipoxygenase inhibitors. Zhongguo Yao Li Xue Bao 1991; 12: 121—125.

14.

Tan HR , Zhang BH Experimental study of the anti-inflammatory effect of matrine. Zhong Xi Yi Jie He Za Zhi 1985; 5: 108—110, 169.

15.

Deng H. , Luo H. , Huang F. et al. Inhibition of proliferation and influence of proto-oncogenes expression by matrine in C6 cell. Zhong Yao Cai 2004; 27: 416—419.

16.

Wang BE Treatment of chronic liver diseases with traditional Chinese medicine. J Gastroenterol Hepatol 2000; 15(Suppl): E67—E70.

17.

Schwarting A. , Wada T. , Kinoshita K. et al. IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice. J Immunol 1998; 161: 494—503.

18.

Ng WL , Chu CM , Wu AK et al. Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus. QJM 2006; 99: 37—47.