Morris M M, Dyson H, Baker D, Harbige L S, Fazakerley J K, Amor S
Immunology Department, Rayne Institute, United Medical and Dental School of Guy's and St. Thomas' Hospital, London, UK.
J Neuroimmunol. 1997 Apr;74(1-2):185-97. doi: 10.1016/s0165-5728(96)00786-2.
Cytokines are important mediators in the pathogenesis of central nervous system (CNS) inflammatory diseases including multiple sclerosis (MS), experimental allergic encephalomyelitis (EAE), viral encephalitis and virus induced demyelinating diseases. We have used immunohistochemical techniques to characterize the mononuclear cell infiltrate and cytokine profiles in the CNS following infection of mice with the demyelinating A7(74) strain of Semliki Forest virus (SFV), an important viral model of MS. Mononuclear cell infiltrates in the CNS, first observed at 3 days and maximal during clearance of infectious virus, were comprised predominantly of CD8+ lymphocytes. F4/80+ macrophage/microglia and CD45/B220+ B lymphocytes were most numerous during the subsequent phase of demyelination. CD4+ T-lymphocytes were observed at low levels throughout infection. By immunostaining MHC class I, IL-1beta , IL-3 and TGF beta1 were constitutively expressed in normal mice and were upregulated following infection. MHC class II, IL-1alpha, IL-2, IL-2R, TNF-alpha and IL-6 were strongly upregulated in the CNS of SFV-infected mice and mice with chronic relapsing EAE. The spatial and temporal distribution of these cytokines during the course of disease was analysed. Whereas IL-1alpha, IL-1beta, IL-10, and TGF beta1 were observed on day 3 following infection GMCSF, IL-2 and TNF alpha were first apparent at day 7 when the cellular infiltration in the CNS was most intense. In contrast IFN gamma and IL-6 were first observed on day 10 prior to the demyelination phase of disease. Cytokines in the lesions of demyelination suggest a role in the pathogeneisis of myelin damage. Based on cytokine profiles no clear bias of either a Th1 or Th2 response was observed in the CNS during infection.
细胞因子是中枢神经系统（CNS）炎性疾病发病机制中的重要介质，这些疾病包括多发性硬化症（MS）、实验性变应性脑脊髓炎（EAE）、病毒性脑炎和病毒诱导的脱髓鞘疾病。我们运用免疫组化技术，对感染了脱髓鞘性Semliki森林病毒（SFV）A7(74)株（一种重要的MS病毒模型）的小鼠中枢神经系统中的单核细胞浸润和细胞因子谱进行了特征分析。中枢神经系统中的单核细胞浸润最早在第3天观察到，在感染性病毒清除期间达到最大值，主要由CD8 +淋巴细胞组成。F4/80 +巨噬细胞/小胶质细胞和CD45/B220 + B淋巴细胞在随后的脱髓鞘阶段数量最多。在整个感染过程中，CD4 + T淋巴细胞的水平较低。通过免疫染色发现，MHC I类、IL-1β、IL-3和TGFβ1在正常小鼠中组成性表达，感染后上调。MHC II类、IL-1α、IL-2、IL-2R、TNF-α和IL-6在感染SFV的小鼠和慢性复发性EAE小鼠的中枢神经系统中强烈上调。分析了这些细胞因子在疾病过程中的时空分布。感染后第3天观察到IL-1α、IL-1β、IL-10和TGFβ1，而GMCSF、IL-2和TNFα最早在第7天出现，此时中枢神经系统中的细胞浸润最为强烈。相比之下，IFNγ和IL-6最早在疾病脱髓鞘阶段前的第10天观察到。脱髓鞘病变中的细胞因子表明其在髓鞘损伤的发病机制中起作用。基于细胞因子谱，在感染期间中枢神经系统中未观察到明显的Th1或Th2反应偏向。
