Interleukin-12 induces mild experimental allergic encephalomyelitis following local central nervous system injury in the Lewis rat
Interleukin-12 induces mild experimental allergic encephalomyelitis following local central nervous system injury in the Lewis rat
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DOI：
10.1016/s0165-5728(03)00180-2
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发表时间：
2003-07-01
影响因子：
3.3
通讯作者：
Cuzner, ML
中科院分区：
文献类型：
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作者：
Ahmed, Z;Baker, D;Cuzner, ML
创伤性脑损伤后中枢神经系统（CNS）的主要病理特征是损伤部位周围和远处的小胶质细胞活化。脑损伤后腹膜内施用白细胞介素-12（IL-12）导致7%的体重减轻、轻度EAE的临床体征和显著的髓鞘碱性蛋白（MBP）特异性脾细胞增殖。与脑损伤后一周相比，如果立即给予IL-12，无论是在一个或两个部位，就炎性血管周围袖带的数量和小胶质细胞的活化而言，病理学的程度最大。在损伤部位周围观察到巨噬细胞和小胶质细胞上的MHC II类和iNOS，内皮细胞和巨噬细胞上的ICAM-1的特异性免疫染色。一定程度的髓鞘加工是明显的MBP在远离病变的炎性细胞的免疫染色。在用IL-12处理的动物的髓质和脊髓中，还在远离损伤部位处检测到包括巨噬细胞、活化的小胶质细胞、CD 4（+）T细胞和iNOS（+）细胞的炎性袖套。这些结果表明，免疫介导的事件，其中IL-12的产生被刺激，例如病毒感染，叠加在脑损伤上，可以提供MS样病理的触发。(C)2003 Elsevier B. V.保留所有权利。
The major pathological feature in the central nervous system (CNS) following traumatic brain injury is activation of microglia both around and distant from the injury site. intraperitoneal administration of interleukin-12 (IL-12) after brain injury resulted in a 7% weight loss, clinical signs of mild EAE and significant myelin basic protein (MBP)-specific splenic cell proliferation. The extent of pathology, in terms of the number of inflammatory perivascular cuffs and activation of microglia was greatest if IL-12 was administered immediately compared to a week following brain injury, whether at one or two sites. Specifically immunostaining for MHC class II and iNOS on macrophages and microglia, ICAM-1 on endothelial cells and macrophages was observed around the site of injury. A degree of myelin processing was apparent from immunostaining of MBP in inflammatory cells distant from the lesion. Inflammatory cuffs comprising macrophages, activated microglia, CD4(+) T cells and iNOS(+) cells were also detected distant to the injury site in the medulla and spinal cord of animals treated with IL-12. These results suggest that immune-mediated events in which IL-12 production is stimulated as for example viral infection, superimposed on a brain injury, could provide a trigger for a MS-like pathology. (C) 2003 Elsevier B.V. All rights reserved.