Department of Pediatrics, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Front Immunol. 2021 Sep 9;12:700903. doi: 10.3389/fimmu.2021.700903. eCollection 2021.
The activation of the sympathetic nervous system, release of norepinephrine (NE), and adrenergic receptor signaling participate in and regulate the complicated enterovirus 71 (EV71) brainstem encephalitis (BE). The neurotoxin 6-hydroxydopamine (6-OHDA) selectively ablates sympathetic nerves and markedly depletes NE in innervated organs. Changes in the plasma levels of NE, severity score, cytokine profiles, and percentages of immunophenotype expression in 7-day-old Bltw : CD1 (ICR) mice infected with EV71, with or without 6-OHDA treatment, were compared. The survival rate (76.9%) of EV71-infected and 6-OHDA (30 μg/g)-treated mice was increased significantly. The clinical scores were decreased markedly on days 8-12 in MP4-infected and 6-OHDA-treated mice compared to those without treatment. The results showed that the plasma levels of NE, epinephrine, and dopamine were decreased on days 4-8 after 6-OHDA treatment and at most on day 8. The plasma levels of interleukin (IL)-12p70, tumor necrosis factor, IL-6, and IL-10 did not change significantly after 6-OHDA treatment. Interferon-γ levels decreased evidently on days 4, 6, and 8 after 6-OHDA treatment. The absolute events of CD3CD4, CD3CD8, and CD3NK1.1 cells of peripheral blood mononuclear cells were increased significantly in MP4-infected and 6-OHDA-treated mice compared to those without treatment. In splenocytes, the absolute cells of CD3NK1.1, CD3NK1.1 and CD11bGr-1 cells of EV71-infected mice were increased significantly after 6-OHDA treatment. These findings suggested that 6-OHDA may be used a probe to explore clinical improvements and immune responses in the complicated EV71 infection. Taken together, peripheral chemical sympathectomy contribute to further understand the immunopathogenesis of EV71 BE with autonomic nervous system dysregulation.
交感神经系统的激活、去甲肾上腺素（NE）的释放和肾上腺素能受体信号参与并调节复杂的肠道病毒 71（EV71）脑干脑炎（BE）。神经毒素 6-羟多巴胺（6-OHDA）选择性地破坏交感神经，显著耗尽受神经支配器官中的 NE。比较了感染 EV71 的 7 日龄 Bltw：CD1（ICR）小鼠（有或没有 6-OHDA 治疗）的血浆 NE 水平变化、严重程度评分、细胞因子谱和免疫表型表达百分比。感染 EV71 且用 6-OHDA（30μg/g）治疗的小鼠的存活率（76.9%）显著增加。与未治疗的小鼠相比，MP4 感染且用 6-OHDA 治疗的小鼠在第 8-12 天临床评分显著降低。结果表明，在 6-OHDA 治疗后第 4-8 天和最多第 8 天，血浆 NE、肾上腺素和多巴胺水平降低。在 6-OHDA 治疗后，白细胞介素（IL）-12p70、肿瘤坏死因子、IL-6 和 IL-10 的血浆水平没有明显变化。干扰素-γ水平在 6-OHDA 治疗后第 4、6 和 8 天明显下降。MP4 感染且用 6-OHDA 治疗的小鼠外周血单个核细胞中 CD3CD4、CD3CD8 和 CD3NK1.1 细胞的绝对事件明显增加，与未治疗的小鼠相比。在脾细胞中，EV71 感染小鼠的 CD3NK1.1、CD3NK1.1 和 CD11bGr-1 细胞的绝对细胞在 6-OHDA 治疗后明显增加。这些发现表明，6-OHDA 可用作探索复杂 EV71 感染中临床改善和免疫反应的探针。综上所述，外周化学交感神经切除术有助于进一步了解 EV71 BE 伴自主神经系统失调的免疫发病机制。
