Interleukin-6-deficient mice resist development of autoimmune myocarditis associated with impaired upregulation of complement C3
Interleukin-6-deficient mice resist development of autoimmune myocarditis associated with impaired upregulation of complement C3
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DOI：
10.1161/01.cir.0000043802.38699.66
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发表时间：
2003-01-21
期刊：
影响因子：
37.8
通讯作者：
Kopf, M
中科院分区：
文献类型：
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作者：
Eriksson, U;Kurrer, MO;Kopf, M
背景-白细胞介素6(IL-6)调节免疫反应的各个方面。在心脏疾病的背景下，它被认为是扩张型心肌病的预后因素，这种疾病通常是由心肌炎引起的。方法和结果：利用IL-6缺陷小鼠，我们研究了IL-6在心肌α-肌球蛋白多肽免疫所致的自身免疫性心肌炎模型中的作用。在没有IL-6的情况下，心肌炎的患病率和严重程度显著降低。来自免疫的IL-6缺陷小鼠的CD4(+)T细胞在体外用特定抗原重新刺激时增殖不良，并且在过继转移到缺乏B细胞和T细胞的IL-6-RAG-2缺陷小鼠中不能介导疾病。IL-6(+/+)小鼠免疫后补体C3的产生在IL-6(+/+)组明显上调，而IL-6缺陷小鼠则无明显上调。结论：IL-6在自身免疫性CD4(+)T细胞的扩增和自身免疫性心肌炎的发病机制中是必需的，可能与补体C3上调有关。
Background-Interleukin (IL)-6 regulates various aspects of the immune response. In the context of heart diseases, it has been recognized as a prognostic factor for dilated cardiomyopathy, which often results from myocarditis.Methods and Results-Using IL-6-deficient mice, we studied the role of IL-6 in a model of autoimmune myocarditis resulting from immunization with a peptide derived from cardiac a-myosin. Prevalence and severity of myocarditis were markedly reduced in the absence of IL-6. CD4(+) T cells from immunized IL-6-deficient mice proliferated poorly on restimulation with specific antigen in vitro and did not mediate disease on adoptive transfer into IL-6-competent RAG-2-deficient mice, which otherwise lack B cells and T cells. Production of complement C3, a crucial factor for the development of myocarditis, was strongly upregulated in IL-6(+/+) but not in IL-6-deficient mice after immunization.Conclusions-Our results demonstrate that IL-6 is required for the expansion of autoimmune CD4(+) T cells and the pathogenesis of autoimmune myocarditis, possibly by upregulation of complement C3.