IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination that involves the down-regulation of the IL-4 receptor in the hippocampus
IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination that involves the down-regulation of the IL-4 receptor in the hippocampus
复制标题
IL-4 介导新生儿乙型肝炎疫苗接种引起的迟发性神经行为损伤，涉及海马 IL-4 受体的下调
DOI：
10.1016/j.cyto.2018.04.037
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Yao Zhibin
中科院分区：
文献类型：
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作者：
Wang Xiao;Yang Junhua;Xing Zhiwei;Zhang Hongyang;Wen Yaru;Qi Fangfang;Zuo Zejie;Xu Jie;Yao Zhibin
我们先前已经证实，新生儿接种乙肝疫苗会导致小鼠海马神经炎症和行为障碍。然而，这些影响的确切机制仍不清楚。在这项研究中，我们观察到新生儿接种乙肝疫苗在血清和海马区诱导了持续4-5 周的抗炎细胞因子反应，主要表现为IL-4水平升高。然而，在接种计划三周后，乙肝疫苗(乙肝)小鼠表现出延迟的海马神经炎症。在外围，IL-4是该疫苗诱导的主要细胞因子。相关分析显示，乙肝小鼠血清和海马区IL-4水平呈正相关。因此，我们调查了新生儿过度暴露于全身IL-4是否会影响大脑和行为。我们观察到，早期经腹腔注射重组小鼠白介素4(mIL-4)的小鼠具有与新生儿接种乙肝疫苗相似的神经炎症和认知障碍。接下来，通过一系列实验探索了IL-4对小鼠大脑影响的机制。总之，这些实验表明，IL-4介导了新生儿接种乙肝疫苗所致的迟发性神经行为损害，包括新生儿血脑屏障的通透性和IL-4受体的下调。这一发现表明，与新生儿IL-4过度暴露有关的临床事件，包括新生儿接种乙肝疫苗和人类婴儿过敏性哮喘，可能会对大脑发育和认知产生不利影响。
We have previously verified that neonatal hepatitis B vaccination induced hippocampal neuroinflammation and behavior impairments in mice. However, the exact mechanism of these effects remain unclear. In this study, we observed that neonatal hepatitis B vaccination induced an anti-inflammatory cytokine response lasting for 4–5 weeks in both the serum and the hippocampus, primarily indicated by elevated IL-4 levels. Three weeks after the vaccination schedule, however, hepatitis B vaccine (HBV)-mice showed delayed hippocampal neuroinflammation. In periphery, IL-4 is the major cytokine induced by this vaccine. Correlation analyses showed a positive relationship in the IL-4 levels between serum and hippocampus in HBV-mice. Thus, we investigated whether neonatal over-exposure to systemic IL-4 influences brain and behavior. We observed that mice injected intraperitoneally with recombinant mouse IL-4 (mIL-4) during early life had similar neuroinflammation and cognition impairment similar to those induced by neonatal hepatitis B vaccination. Next, the mechanism underlying the effects of IL-4 on brain in mice was explored using a series of experiments. In brief, these experiments showed that IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination, which involves the permeability of neonatal blood–brain barrier and the down-regulation of IL-4 receptor. This finding suggests that clinical events concerning neonatal IL-4 over-exposure, including neonatal hepatitis B vaccination and allergic asthma in human infants, may have adverse implications for brain development and cognition.