Overexpression of interleukin-6 aggravates viral myocarditis:: Impaired increase in tumor necrosis factor-α
Overexpression of interleukin-6 aggravates viral myocarditis:: Impaired increase in tumor necrosis factor-α
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DOI：
10.1006/jmcc.2001.1428
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发表时间：
2001-09-01
影响因子：
5
通讯作者：
Kurabayashi, M
中科院分区：
文献类型：
--
作者：
Tanaka, T;Kanda, T;Kurabayashi, M
炎症和免疫反应的过程受促炎症细胞因子的调节。白介素6(IL-6)。一种促炎细胞因子。在病毒性心肌炎中起着潜在的关键作用。我们以前的工作证明，外源性IL-6在C3H/HEJ小鼠接种脑心肌炎病毒(EMCV)时给予。对心肌有保护作用，提高存活率。在本研究中。我们检测IL-6的过度表达是否可以改变病毒性心肌炎。在接种EMCV后第3天和第10天，IL-6转基因小鼠(IL-6TG)的心脏重量/体重比和心肌损伤明显增加。在第3天，病毒清除的减少表现为病毒滴度的升高和IL-6TG中心的病毒复制。而野生型小鼠血清肿瘤坏死因子-α(TNF-α)浓度在第1天显著升高。IL-6TG无此变化。重组人肿瘤坏死因子(2杯)治疗显著改善了IL-6TG心脏中的病毒清除。因此，IL-6的过度表达通过中断细胞因子网络和病毒清除来促进心肌损伤。这些实验表明，IL-6可能是加速组织损伤的因素之一。包括心肌损伤，在病毒性心肌炎中。(C)2001年学术出版社。
The process of inflammation and immune response is regulated by proinflammatory cytokines. Interleukin-6 (IL-6). one of the proinflammatory cytokines. plays a potentially critical role in viral-induced myocarditis. Our previous work demonstrates that exogenous IL-6 administration, given at the time of encephalomyocarditis virus (EMCV) inoculation in C3H/HeJ mice. has it protective effect on myocardium and improves survival rates. In the present study. we examined whether overexpression of IL-6 modified viral myocarditis. On day 3 and 10 after inoculation with EMCV the ratio of heart weight to body weight and myocardial injury were significantly increased in IL-6 transgenic mice (IL-6TG). On day 3. a reduction of viral clearance was shown by the presence of elevated viral titers and viral replication in the heart of IL-6TG. The concentrations of serum tumor necrosis factor-alpha (TNF alpha) were dramatically increased in wild-type mice on day 1. in contrast. this change was not observed in IL-6TG. Treatment with recombinant human TNF (2 mug) significantly improved viral clearance in the IL-6TG hearts. Thus, overexpression of IL-6 promotes myocardial injury by interrupting both the cytokine network and viral clearance. These experiments suggest the possibility that IL-6 is one of the factors that accelerates tissue damage. including myocardial injury, in the viral myocarditis. (C) 2001 Academic Press.