Wesselingh S L, Levine B, Fox R J, Choi S, Griffin D E
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
J Immunol. 1994 Feb 1;152(3):1289-97.
Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent inflammatory response is first detected 3 days after infection and includes T cells, B cells, and macrophages. The cytokines produced locally by intrinsic cells of the brain in response to infection and by infiltrating mononuclear cells and their contributions to outcome of infection have not been identified. Semiquantitative reverse transcriptase-PCR was used to evaluate the expression of mRNAs for IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, leukemia inhibitory factor (LIF), and TGF-beta in the brain during fatal and nonfatal SV encephalitis of immunocompetent BALB/cJ and immunodeficient scid/CB17 mice. IL-1 beta and IL-6 mRNAs were detected in uninfected mice before infection and were up-regulated within 24 h. TGF-beta mRNA was also constitutively expressed in uninfected mice. LIF mRNA was occasionally detected in uninfected mice but increased in amounts only in BALB/cJ not scid mice after infection. TNF-alpha, IL-4, and IL-10 mRNAs were not found in uninfected mice but were induced within 24 h and continued to rise through 7 days after infection with substantially higher levels in BALB/cJ than scid mice. These data suggest that intrinsic brain cells produce IL-1, IL-4, IL-6, IL-10, LIF, and TGF-beta mRNAs in response to viral infection. IFN-gamma and IL-2 mRNAs were detected only in BALB/cJ mice and not until 3 days after infection with the initiation of inflammation. IL-4 and IL-10 mRNAs were more persistent and more easily detectable than IL-2 and IFN-gamma mRNAs. These data suggest a predominant type 2 cytokine response in the brain during SV encephalitis. BALB/cJ mice infected with a neurovirulent strain of SV (NSV), had 100% mortality, whereas NSV-infected scid mice developed persistent nonfatal infection. Inflammation was more intense in NSV-infected mice, however, no substantial differences in cytokine mRNA levels were detected when compared with mice with nonfatal SV infection suggesting that the cytokines measured do not in and of themselves lead to fatal central nervous system disease.
辛德毕斯病毒（SV）可在小鼠中引发急性脑脊髓炎。感染后3天首次检测到T细胞依赖性炎症反应，包括T细胞、B细胞和巨噬细胞。大脑固有细胞对感染的反应以及浸润的单核细胞产生的细胞因子及其对感染结果的影响尚未明确。采用半定量逆转录聚合酶链反应（RT-PCR）评估免疫活性BALB/cJ小鼠和免疫缺陷scid/CB17小鼠在致命性和非致命性SV脑脊髓炎期间大脑中白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）、白血病抑制因子（LIF）和转化生长因子-β（TGF-β）的mRNA表达。在未感染的小鼠感染前检测到IL-1β和IL-6的mRNA，且在24小时内上调。TGF-β的mRNA在未感染的小鼠中也有组成性表达。LIF的mRNA在未感染的小鼠中偶尔检测到，但仅在感染后的BALB/cJ小鼠中而非scid小鼠中数量增加。未感染的小鼠中未发现TNF-α、IL-4和IL-10的mRNA，但在感染后24小时内被诱导，并在感染后7天内持续上升，BALB/cJ小鼠中的水平显著高于scid小鼠。这些数据表明大脑固有细胞对病毒感染产生IL-1、IL-4、IL-6、IL-10、LIF和TGF-β的mRNA。仅在BALB/cJ小鼠中检测到干扰素-γ（IFN-γ）和IL-2的mRNA，且直到感染后3天炎症开始时才检测到。IL-4和IL-10的mRNA比IL-2和IFN-γ的mRNA更持久且更容易检测到。这些数据表明在SV脑脊髓炎期间大脑中主要存在2型细胞因子反应。感染神经毒力株SV（NSV）的BALB/cJ小鼠死亡率为100%，而感染NSV的scid小鼠则发展为持续性非致命感染。然而，NSV感染的小鼠炎症更强烈，与非致命性SV感染的小鼠相比，细胞因子mRNA水平未检测到实质性差异，这表明所检测的细胞因子本身不会导致致命的中枢神经系统疾病。
