Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation.
Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation.
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DOI：
10.1186/1743-422x-8-17
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发表时间：
2011-01-14
期刊：
影响因子：
4.8
通讯作者：
Yanlan H
中科院分区：
文献类型：
--
作者：
Fan Y;Weifeng W;Yuluan Y;Qing K;Yu P;Yanlan H
近年来，一些研究表明白细胞介素（IL）-17（IL-17）是一种T细胞（Th 17）源性的促炎细胞因子，是炎症和自身免疫性疾病中组织炎症的主要介质。病毒性心肌炎（VMC）是一种T细胞介导的自身免疫性疾病，但IL-17在VMC中的作用尚未明确。用IL-17单克隆抗体（IL-17 mAb）处理的VMC小鼠，检测IL-17在VMC发病中的作用。在注射柯萨奇病毒B3（CVB 3）后3天，用大鼠抗鼠IL-17单克隆抗体（抗IL-17）或大鼠IgG 2A同种型对照或磷酸盐缓冲液处理VMC小鼠。正常对照组为未做任何处理的正常小鼠。监测小鼠存活率并进行心脏病理组织学检查。半定量RT-PCR检测心肌组织IL-17、IL-6和TNF-α mRNA的表达。采用酶联免疫吸附法检测全身IL-17、IL-6和TNF-α水平，采用免疫组化法检测局部心肌IL-17表达。流式细胞仪检测CD 4 +T细胞中Th 17亚群的分布。结果表明，用抗IL-17中和IL-17可改善临床症状，延缓病程，降低血清IL-17水平，而不降低IL-17、IL-6、TNF-α mRNA转录水平和血清IL-6、TNF-α水平。Th 17细胞的分化和增殖没有变化。提示IL-17在小鼠VMC发病中起重要作用，抑制IL-17可减轻VMC后的心肌炎症反应。
Recently, some studies indicate that interleukin (IL)-17, known as a T cell (Th17)-derived proinflammatory cytokine, is the major mediator of tissue inflammation in inflammatory and autoimmune diseases. Viral myocarditis (VMC) is a T cell-mediated autoimmune disease, but the role for IL-17 in VMC is not well defined. Using IL-17 monoclonal antibody (IL-17mAb)-treated VMC mice, we tested the pathogenic role of IL-17 in the development of VMC. VMC mice were treated with monoclonal rat anti-murine IL-17 antibody (anti-IL-17) or rat IgG2A isotype control or phosphate-buffered solution 3 days after Coxsackievirus B3 (CVB3) injection. Normal mice without any manipulation were taken as normal control. The survival rates of mice were monitored and heart pathology was examined histologically. IL-17, IL-6, and TNF-α mRNA of the myocardium were assessed by semi-quantitative RT-PCR. Systemic IL-17, IL-6, and TNF-α level were measured by enzyme-linked immunosorbent assay, and local myocardium IL-17 expression was analyzed using immunohistochemical staining. Flow cytometric analysis was used to evaluate the frequencies of Th17 subsets in CD4+T cells. Results showed that neutralization of IL-17 with anti-IL-17 can ameliorate clinical symptoms, defer disease course, decrease serum IL-17 level, without declining the IL-17, IL-6 and TNF-α mRNA transcript level and serum IL-6, TNF-α level. The differentiation and proliferation of the Th17 cells were unchanged. Our data suggest that IL-17 is crucially involved in the pathogenesis of murine VMC, IL-17 inhibition might ameliorate the myocardium inflammation after the onset of VMC.