Abstract：
Japanese encephalitis virus (JEV) infection is considered a global public health emergency. Severe peripheral neuropathy caused by JEV infection has increased disability and mortality rates in recent years. Because there are very few therapeutic options for JEV infection, prompt investigations of the ability of clinically safe, efficacious and globally available drugs to inhibit JEV infection and ameliorate peripheral neuropathy are urgently needed. In this study, we found that high doses of intravenous immunoglobulin, a function inhibitor of acid sphingomyelinase (FIASMA), inhibited acid sphingomyelinase (ASM) and ceramide activity in the serum and sciatic nerve of JEV-infected rats, reduced disease severity, reversed electrophysiological and histological abnormalities, significantly reduced circulating proinflammatory cytokine levels, inhibited Th1 and Th17 cell proliferation, and suppressed the infiltration of inflammatory CD4 + cells into the sciatic nerve. It also maintained the peripheral nerve-blood barrier without causing severe clinical side effects. In terms of the potential mechanisms, ASM was found to participate in immune cell differentiation and to activate immune cells, thereby exerting proinflammatory effects. Therefore, immunoglobulin is a FIASMA that reduces abnormal immune responses and thus targets the ASM/ceramide system to treat peripheral neuropathy caused by JEV infection.
摘要：
日本脑炎病毒（JEV）感染被认为是全球公共卫生紧急情况。近年来，由JEV感染引起的严重周围神经病变增加了残疾和死亡率。因为JEV感染的治疗选择很少，迅速调查临床安全的能力，目前迫切需要有效和全球可获得的药物来抑制JEV感染和改善周围神经病变。在这项研究中,我们发现高剂量的静脉注射免疫球蛋白，酸性鞘磷脂酶（FIASMA）的功能抑制剂，抑制JEV感染大鼠血清和坐骨神经中的酸性鞘磷脂酶（ASM）和神经酰胺活性，降低疾病严重程度，逆转电生理和组织学异常，显著降低循环促炎细胞因子水平，抑制Th1和Th17细胞增殖，并抑制炎性CD4+细胞向坐骨神经的浸润。它还维持了周围神经-血液屏障，而不会引起严重的临床副作用。就潜在机制而言，发现ASM参与免疫细胞分化并激活免疫细胞，从而发挥促炎作用。因此,免疫球蛋白是一种减少异常免疫反应的FIASMA，因此靶向ASM/神经酰胺系统来治疗由JEV感染引起的周围神经病变。
