A pilot study of the therapeutic efficacy and mechanism of artesunate in the MRL/lpr murine model of systemic lupus erythematosus.
Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease. In this study, we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model. MRL/lpr mice were divided into control, cyclophosphamide (CTX) and artesunate treatment groups. Blood was collected to measure serum levels of creatinine, antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody. Twenty-four-hour urine was collected to measure levels of proteinuria. The concentration of monocyte chemotactic protein-1 (MCP-1) in serum and urine was measured. The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay, respectively. The expression of B cell activating factor (BAFF) in spleen was determined by real time-PCR and immunoblotting. We found that artesunate significantly increased the survival rate, body weight and blood leukocyte counts, and reduced the serum levels of ANA and anti-dsDNA antibody titer, 24 h urinary protein, and serum creatinine. Our results indicated that artesunate could decrease MCP-1, major pro-inflammation cytokine, in serum, urine and kidney. We also found that the level of BAFF, the major B cell activation factor, was decreased in artesunate treated MRL/lpr mice. Its efficacy was comparable with that of CTX in this study. Taken together, we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.
Jin
Ouyang
O
Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.
Zhang
Huayong
H
Gu
Zhifeng
Z
Zhao
Shengnan
S
Xu
Ting
T
Zhou
Kangxing
K
Jiang
Bo
B
Wang
Jie
J
Zeng
Xiaofeng
X
Sun
Lingyun
L
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology; D001835:Body Weight; D018932:Chemokine CCL2 / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007962:Leukocytes / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D010865:Pilot Projects; D011507:Proteinuria / Q000652:urine
D000974:Antibodies, Antinuclear; D037621:Artemisinins; D053264:B-Cell Activating Factor; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C505720:Tnfsf13b protein, mouse; D000077332:Artesunate