Central nervous system-initiated inflammation and neurotrophism in trauma:: IL-1β is required for the production of ciliary neurotrophic factor
Central nervous system-initiated inflammation and neurotrophism in trauma:: IL-1β is required for the production of ciliary neurotrophic factor
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DOI：
10.4049/jimmunol.165.4.2232
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发表时间：
2000-08-15
影响因子：
4.4
通讯作者：
Yong, VW
中科院分区：
文献类型：
--
作者：
Herx, LM;Rivest, S;Yong, VW
CNS损伤导致炎性细胞因子在该组织内产生和积累。CNS内炎症的起源和作用仍然存在争议。在本文中，我们证明了小鼠脑的急性创伤导致IL-1 β的快速升高，这种增加在损伤后15分钟可检测到，并且显著先于数小时后发生的白细胞流入。为了证实IL-1 β上调是由CNS内的细胞启动的，将细胞因子转录物的原位杂交与细胞类型免疫组织化学相结合。结果显示，在损伤后3小时，实质小胶质细胞是IL-1 β的唯一来源。通过检测神经营养因子睫状神经营养因子（CNTF）的表达来阐明CNS引发的炎症的作用。首先，在病变部位应用IL-1受体拮抗剂减弱了CNTF的上调。其次，检查遗传性IL-1 β缺陷的皮质切除动物未发现CNTF上调。第三，通过将IL-1 β外源性应用于损伤部位，挽救了IL-1 β缺失小鼠中CNTF升高的缺乏。这些发现提供了CNS创伤后CNTF产生需要IL-1 β的第一个证据，并表明炎症对CNS的再生能力有有益的影响。
Injury to the CNS results in the production and accumulation of inflammatory cytokines within this tissue. The origin and role of inflammation within the CNS remains controversial. In this paper we demonstrate that an acute trauma to the mouse brain results in the rapid elevation of IL-1 beta, This increase is detectable by 15 min after injury and significantly precedes the influx of leukocytes that occurs hours after. To confirm that IL-1 beta up-regulation is initiated by cells within the CNS, in situ hybridization for cytokine transcript was combined with cell type immunohistochemistry. The results reveal parenchymal microglia to be the sole source of IL-1 beta at 3 h postinjury, A role for CNS-initiated inflammation was addressed by examining the expression of the neurotrophic factor, ciliary neurotrophic factor (CNTF), Analysis of their temporal relationship suggests the up-regulation of CNTF by IL-1 beta, which was confirmed through three lines of evidence. First, the application of IL-1 receptor antagonist into the lesion site attenuated the up-regulation of CNTF, Second, the examination of corticectomized animals genetically deficient for IL-1 beta found no CNTF up-regulation. Third, the lack of CNTF elevation in IL-1 beta null mice was rescued through exogenous application of IL-1 beta into the lesion site. These findings provide the first evidence of the requirement for IL-1 beta in the production of CNTF following CNS trauma, and suggest that inflammation can have a beneficial impact on the regenerative capacity of the CNS.