CYTOKINE PRODUCTION IN THE CENTRAL-NERVOUS-SYSTEM OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - DYNAMICS OF MESSENGER-RNA EXPRESSION FOR INTERLEUKIN-10, INTERLEUKIN-12, CYTOLYSIN, TUMOR-NECROSIS-FACTOR-ALPHA AND TUMOR-NECROSIS-FACTOR-BETA
CYTOKINE PRODUCTION IN THE CENTRAL-NERVOUS-SYSTEM OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - DYNAMICS OF MESSENGER-RNA EXPRESSION FOR INTERLEUKIN-10, INTERLEUKIN-12, CYTOLYSIN, TUMOR-NECROSIS-FACTOR-ALPHA AND TUMOR-NECROSIS-FACTOR-BETA
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DOI：
10.1016/0165-5728(95)00100-g
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发表时间：
1995-09-01
影响因子：
3.3
通讯作者：
OLSSON, T
中科院分区：
文献类型：
--
作者：
ISSAZADEH, S;LJUNGDAHL, A;OLSSON, T
本文研究了刘易斯大鼠实验性自身免疫性脑脊髓炎（EAE）过程中中枢神经系统（CNS）一系列促病和限病细胞因子mRNA表达的动态变化。用合成的寡核苷酸探针原位杂交技术检测脊髓冰冻切片中表达细胞因子mRNA的细胞。细胞因子mRNA的表达可分为三个阶段：（i）白细胞介素（IL）-12，肿瘤坏死因子（TNF）-β（ii）TNF-α在EAE临床体征高峰时达到峰值;（iii）IL-10在临床恢复时和临床恢复后出现增加。先前显示的IL-12在干扰素-γ（IFN-γ）mRNA表达之前的早期表达与IL-12在促进产生IFN-γ的T辅助1（Th 1）型细胞的增殖和活化中的作用一致。在临床症状出现之前TNF-β mRNA的表达有利于这种细胞因子在疾病发生中的作用。TNF-α mRNA表达与EAE的临床症状密切相关，这些观察结果提示TNF-α的致病效应作用。对于溶细胞素也可能是这种情况。IL-10表达细胞在EAE的恢复期逐渐增加到高水平，与下调CNS炎症的功能一致。从这些数据中，我们得出结论，有一个有序的外观推定的疾病促进和限制细胞因子在中枢神经系统在急性EAE。
The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected in cryosections of spinal cords using in situ hybridization technique with synthetic oligonucleotide probes, Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (=lymphotoxin-alpha) and cytolysin appeared early and before onset of clinical signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previously is consistent with a role of IL-12 in promoting proliferation and activation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF-beta mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA expression roughly paralleled the clinical signs of EAE. This may be the case also for cytolysin. IL-10-expressing cells gradually increased to high levels in the recovery phase of EAE, consistent with a function in down-regulating the CNS inflammation. From these data we conclude that there is an ordered appearance of putative disease-promoting and -limiting cytokines in the CNS during acute monophasic EAE.