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急性病毒性脑脊髓炎小鼠中枢神经系统中细胞因子的产生及作用

Production and role of cytokines in the CNS of mice with acute viral encephalomyelitis.

作者信息

Mokhtarian F, Wesselingh S L, Choi S, Maeda A, Griffin D E, Sobel R A, Grob D

机构信息

Department of Medicine, SUNY Health Science Center/Maimonides Medical Center, Brooklyn, 11219 USA.

出版信息

J Neuroimmunol. 1996 May;66(1-2):11-22. doi: 10.1016/0165-5728(95)00181-6.

DOI:10.1016/0165-5728(95)00181-6
PMID:8964904
Abstract

Semliki Forest Virus (SFV) causes a more severe acute encephalomyelitis in B6 than in SJL mice despite similar T cell proliferation and antibody responses in these two strains. To determine the immunological mechanisms that may contribute to this difference, CNS tissues from SFV-infected B6 and SJL mice were analyzed for viral replication, inflammatory responses and cytokine production, by semiquantitative reverse transcriptase-PCR and immunohistochemistry. Although initially similar on day 2 p.i., SFV replicated to higher viral titers in B6 than SJL mice on days 4 and 7 p.i. Infectious virus was cleared from both strains by day 10 p.i. There were no differences in numbers of CD4+, CD8+ or MHC class I and II+ inflammatory cells at any time point. Higher levels of IL-4 mRNA, lower levels of TNF-alpha, IL-6, IL-1 beta and IL-2 mRNAs and lower IL-2+ and IFN-gamma+ cells were found in B6. These findings suggest that despite comparable immune responses, different patterns of cytokine production correlated with higher levels of virus in the brains and more severe clinical disease in B6, and more efficient clearance of virus and less severe disease in SJL mice.

摘要

塞姆利基森林病毒(SFV)在B6小鼠中引发的急性脑脊髓炎比在SJL小鼠中更为严重,尽管这两种品系的T细胞增殖和抗体反应相似。为了确定可能导致这种差异的免疫机制,通过半定量逆转录聚合酶链反应和免疫组织化学分析了感染SFV的B6和SJL小鼠的中枢神经系统组织中的病毒复制、炎症反应和细胞因子产生情况。虽然在感染后第2天最初相似,但在感染后第4天和第7天,SFV在B6小鼠中的复制病毒滴度高于SJL小鼠。到感染后第10天,两种品系的传染性病毒均被清除。在任何时间点,CD4 +、CD8 +或MHC I类和II类+炎症细胞的数量均无差异。在B6小鼠中发现IL-4 mRNA水平较高,TNF-α、IL-6、IL-1β和IL-2 mRNA水平较低,IL-2 +和IFN-γ +细胞较少。这些发现表明,尽管免疫反应相当,但细胞因子产生的不同模式与B6小鼠脑中较高的病毒水平和更严重的临床疾病相关,而在SJL小鼠中病毒清除更有效且疾病较轻。

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