Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic encephalitis
Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic encephalitis
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DOI：
10.1016/s0165-5728(97)00184-7
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发表时间：
1998-02-01
影响因子：
3.3
通讯作者：
Sriram, S
中科院分区：
文献类型：
--
作者：
Bright, JJ;Musuro, BF;Sriram, S
EAE是一种Th 1细胞介导的中枢神经系统炎性自身免疫性脱髓鞘疾病。IL-12是一种70 kd的异源二聚体细胞因子，能够调节广泛的免疫功能。鉴于IL-12 p40在Th 1免疫反应发展中的关键作用，我们研究了IL-12 p40在EAE小鼠中枢神经系统和淋巴器官中的表达。RT-PCR分析显示IL-12 p40在EAE急性麻痹期脑和脊髓中的表达增加，在临床恢复后降低。在疾病高峰期，脾脏、淋巴结和肝脏中p40 mRNA的表达也随着循环血清IL-12水平的升高而增加。rIL-12的体内给药增加了MBP致敏的T细胞的增殖反应和IFN-γ的产生，并且在用抗IL-12抗体治疗后降低。IL-12在EAE动物的靶器官和淋巴器官中的表达，神经元抗原免疫后诱导的Th 1型免疫应答以及抗IL-12抗体治疗后对临床疾病的抑制，表明IL-12在EAE发病机制中的关键作用。(C)1998年Elsevier Science B.V.
EAE is a Th1 cell-mediated inflammatory autoimmune demyelinating disease of the central nervous system. IL-12 is a 70 kd heterodimeric cytokine, capable of regulating a wide range of immune functions. In view of its crucial role in the development of Th1 immune responses, we studied the expression of IL-12 p40 in the CNS and lymphoid organs of mice with EAE. RT-PCR analysis showed an increase in the expression of IL-12 p40 in brain and spinal cord during the acute paralytic phase of EAE and that decreased upon clinical recovery. The expression of p40 mRNA was also increased in spleen, lymph node and liver along with an elevated levels of circulating serum IL-12 during the height of disease. In vivo administration of rIL-12 increased the proliferative response and IFN-gamma production of MBP sensitized T cells and that was decreased following treatment with anti-IL-12 antibody. The expression of IL-12 in the target and lymphoid organs of animals with EAE, the induction of a Th1 type immune response following immunization with neuronal antigens and the inhibition of clinical disease upon treatment with anti-IL-12 antibody, suggest the crucial role of IL-12 in the pathogenesis of EAE. (C) 1998 Elsevier Science B.V.