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学科主题: 临床医学
题名:
Effects of atorvastatin on the Th1/Th2 polarization of ongoing experimental autoimmune myocarditis in Lewis rats
作者: Liu, W; Li, WM; Gao, C; Sun, NL
关键词: EAM ; idiopathic dilated cardiomyopathy ; HMG-CoA reductase inhibitor ; Th1/Th2 autoimmunity
刊名: JOURNAL OF AUTOIMMUNITY
发表日期: 2005-12-01
DOI: 10.1016/j.jaut.2005.06.005
卷: 25, 期:4, 页:258-263
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology
研究领域[WOS]: Immunology
关键词[WOS]: STATINS ; PARALYSIS ; DISEASE
英文摘要:

Objective: Experimental autoimmune myocarditis (EAM) in rats is it T cell-mediated disorder and the involvement of Th1/Th2 unbalance has been demonstrated. This Study was designed to test the hypothesis that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, affects T cell-mediated autoimmunity through modulating the balance of Th1/Th2 and reduces the severity of EAM.

Methods: Myocarditis was induced in 23 Lewis rats by injection of porcine cardiac myosin. High-dose (10 mg/kg/day) or low-dose (1 mg/kg/day) atorvastatin or vehicle was administered orally for 3 weeks to rats with EAM at the same time Of irunnInization. Seven Lewis rats received neither immunization nor statins therapy were used as normal controls. On day 21 after immunization (the climax of inflammation), echocardiography was examined and the severity of myocarditis was evaluated by histopathological evaluation. The area ratio (affected/entire area percentage) of myocardial lesions was determined in histological sections. Heart weight/body weight ratio was determined and the serum lipid levels were measured. Levels of serum IFN-gamma, IL-2, IL-4 and IL-10 were Measured by ELISA.

Results: Cardiac function was improved in the two atorvastatin-treated groups compared to the untreated group. Heart weight/body weight ratio and the degree of inflammation were significantly lower in the two dosage statin-treated groups than that in the untreated one. Furthermore, treatment with atorvastatin decreased the expression levels of Th1 cytokine (IFN-gamma and IL-2), and increased the expression levels of Th2 cytokine (IL-4 and IL-10). Atorvastatin attenuated the histopathological severity of myocarditis. Plasma lipid levels did not differ between the groups.

Conclusions: Atorvastatin ameliorates EAM by inhibiting T cell responses and suppressing Th1-type and inflammatory cytokines production and this activity is independent of cholesterol reduction, whereas Th2-type cytokines production was promoted. Atorvastatin may have beneficial effects on myocarditis by modulating the Th1/Th2 balance. These results demonstrate an important role of Th1/Th2 polarization in the pathogenesis of EAM and suggest that HMG-CoA reductase blockade may be a promising new strategy for the treatment of organ specific autoimmune diseases. (c) 2005 Elsevier Ltd. All rights reserved.

语种: 英语
WOS记录号: WOS:000234157800002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64606
Appears in Collections:北京大学第二临床医学院_心血管内科_期刊论文

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作者单位: 1.Harbin Med Coll, Affiliated Hosp 1, Dept Cardiol, Heilongjiang 150001, Peoples R China
2.Harbin Med Coll, Affiliated Hosp 1, Dept Neurosurg, Heilongjiang 150001, Peoples R China
3.Peking Univ, Peoples Hosp, Dept Cardiol, Beijing 100044, Peoples R China

Recommended Citation:
Liu, W,Li, WM,Gao, C,et al. Effects of atorvastatin on the Th1/Th2 polarization of ongoing experimental autoimmune myocarditis in Lewis rats[J]. JOURNAL OF AUTOIMMUNITY,2005,25(4):258-263.
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