The role of cytokines in autoimmune encephalomyelitis and rejection processes of neural grafts

本研究通过建立实验性自身免疫性脑脊髓炎(EAE)模型和神经组织移植模型，探讨了中枢神经系统(CNS)病变中细胞因子分泌的细胞因子及其网络的作用。由于中枢神经系统中表达的细胞因子蛋白和信使核糖核酸的量很少，因此很难用免疫印迹和Northern印迹等常规方法对其进行检测。相反，我们试图通过建立实验性自身免疫性脑脊髓炎(EAE)和神经组织移植模型，建立细胞因子mRNA的定量分析方法。在急性单相大鼠EAE中，促炎症(干扰素-γ和肿瘤坏死因子-α)和抗炎(IL-10)细胞因子在EAE早期达到最大值，提示其临床过程的本质。另一方面，在移植排斥过程中，穿孔素和颗粒酶B等细胞溶解蛋白的mRNA显著表达。这些疾病特异性细胞因子分泌谱强烈表明，中枢神经系统形成的损伤的性质通过调节脑内形成的细胞因子网络来调节损伤修复的模式。

In the present study, we investigated the role of cytokines secreted in the lesion in the central nervous system (CNS) and cytokine network.Since the amount of cytokine protein and mRNA expressed in the CNS is very little, it was very difficult to examine them by ordinary methods such as Western and Northern blot analysis.Instead, using the experimental autoimmune encephalomyelitis (EAE) and neural tissue grafting model, we tried to establish the quantitative analysis of cytokine mRNA after amplification by the PCR techniques, i.e., competitive PCR.In acute and monophasic rat EAE,both pro-inflammatory )IFN-gamma and TNF-alpha) and anti-inflammatory (IL-10) cytokines reached a maximal at the early stage of EAE suggesting the nature of its clinical course.On the other hand, in the graft rejection processes, mRNA for cytolytic protein such as perforin and granzyme B was expressed markedly.These disease-specific cytokine secretion profile strongly suggest that the nature of the lesion formed in the CNS regulates the mode of the lesion repair by modulating the cytokine network formed in the brain.