Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan; Department of Emergency Medicine, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan; Department of Emergency Medicine, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
Biomed Pharmacother. 2019 Oct;118:109271. doi: 10.1016/j.biopha.2019.109271. Epub 2019 Aug 1.
Enterovirus 71 (EV71) brainstem encephalitis (BE) is divided into-uncomplicated BE, autonomic nervous system (ANS) dysregulation, and pulmonary edema (PE)-based on cytokine-mediated severe systemic and central nervous system (CNS) inflammatory responses. Minocycline has been found to have anti-inflammatory and immunomodulatory properties in infectious and inflammatory neurological disease models. The effects of minocycline on EV71 infection were studied in vitro and in vivo experiments. The minocycline treatment (100-300 μg/mL) on cytokine expressions and viral replications were investigated in rhabdomyosarcoma (RD), U-87MG, and THP-1 cells. The mouse-adapted-EV71 strain (MP4)-infected 7-day-old ICR mice model was used to explore the anti-inflammatory and antiviral effects of minocycline (1 and 5 μg/g) for the treatment of EV71 infection. In in vitro, minocycline reduced cytopathic effects (CPEs), viral protein expressions, viral titers, the levels of interleukin (IL)-6 and IL-8 and relative mRNA expressions of IL-12p40, IL-1β, and tumor necrosis factor (TNF) after EV71 infection. The levels of TNF, IL-1β, IL-6, and IL-8 decreased with a single dose of minocycline in EV71-infected THP-1 cells. Double-dose minocycline treatment demonstrated more effective reduction in cytokines. In the MP4-infected animal model, clinical scores, mortality rates and viral titers in various brain tissues were decreased evidently after double-dose minocycline treatment. Minocycline inhibited IL-6 and granulocyte colony-stimulating factor (G-CSF) in plasma and TNF in the cerebellum. Minocycline has properties that enable it to function both as an anti-inflammatory and antiviral agent in EV71 infection. These results evidence its potential usefulness in clinical treatment.
肠道病毒 71 型（EV71）脑干脑炎（BE）分为单纯 BE、自主神经系统（ANS）失调和肺水肿（PE），这是基于细胞因子介导的严重全身和中枢神经系统（CNS）炎症反应。米诺环素在感染和炎症性神经疾病模型中具有抗炎和免疫调节作用。在体外和体内实验中研究了米诺环素对 EV71 感染的影响。研究了米诺环素（100-300μg/mL）对横纹肌肉瘤（RD）、U-87MG 和 THP-1 细胞中细胞因子表达和病毒复制的影响。采用适应小鼠的 EV71 株（MP4）感染 7 日龄 ICR 小鼠模型，探讨米诺环素（1 和 5μg/g）对 EV71 感染的抗炎和抗病毒作用。在体外，米诺环素降低了细胞病变效应（CPE）、病毒蛋白表达、病毒滴度、白细胞介素（IL）-6 和 IL-8 水平以及 IL-12p40、IL-1β 和肿瘤坏死因子（TNF）的相对 mRNA 表达。在 EV71 感染的 THP-1 细胞中，单次给予米诺环素后，TNF、IL-1β、IL-6 和 IL-8 水平降低。双剂量米诺环素治疗显示出更有效的细胞因子减少。在 MP4 感染的动物模型中，双剂量米诺环素治疗后，临床评分、死亡率和各种脑组织中的病毒滴度明显降低。米诺环素抑制了血浆中的 IL-6 和粒细胞集落刺激因子（G-CSF）以及小脑中的 TNF。米诺环素具有抗炎和抗病毒作用，使其在 EV71 感染中具有潜在的应用价值。这些结果表明其在临床治疗中的有效性。
