Role of IL-1α and IL-1β in ischemic brain damage
Role of IL-1α and IL-1β in ischemic brain damage
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DOI：
10.1523/jneurosci.21-15-05528.2001
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发表时间：
2001-08-01
影响因子：
5.3
通讯作者：
Rothwell, NJ
中科院分区：
文献类型：
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作者：
Boutin, H;LeFeuvre, RA;Rothwell, NJ
细胞因子白细胞介素-1（IL-1）与缺血性脑损伤的发病机制密切相关。本研究的目的是比较短暂性脑缺血[大脑中动脉闭塞（MCAO）30分钟]对野生型（WT）小鼠和IL-1 α、IL-1 β和IL-1 β对神经元损伤的影响。与野生型相比，缺乏两种形式的IL-1的小鼠表现出显著减少的缺血性梗死体积（总体积，70%;皮质，87%减少）。与WT小鼠相比，在单独缺乏IL-1 α或IL-1 β的小鼠中，缺血性损伤没有显著改变。在WT和IL-1 α KO小鼠中，MCAO强烈诱导IL-1 β mRNA，但不诱导IL-1 α或IL-1 1 1型受体。重组IL-1受体拮抗剂（脑室内）显著减少WT（-32%）和IL-1 α KO（-48%）小鼠的梗死体积，但对IL-1 β或IL-1 α/β KO小鼠的损伤没有影响。这些数据证实IL-1在缺血性脑损伤中起主要作用。他们还表明，IL-1 α或IL-1 β的慢性缺失不能影响脑损伤，这可能是由于IL-1 α KO小鼠中IL-1系统的代偿性变化和IL-1 β KO小鼠中神经元死亡的IL-1非依赖性介质的变化。
The cytokine interleukin-1 (IL-1) has been strongly implicated in the pathogenesis of ischemic brain damage. Evidence to date suggests that the major form of IL-1 contributing to ischemic injury is IL-1 beta rather than IL-1 alpha, but this has not been tested directly.The objective of the present study was to compare the effects of transient cerebral ischemia [30 min middle cerebral artery occlusion (MCAO)] on neuronal injury in wild-type (WT) mice and in IL-1 alpha, IL-1 beta, or both IL-1 alpha and IL-1 beta knock-out (KO) mice.Mice lacking both forms of IL-1 exhibited dramatically reduced ischemic infarct volumes compared with wild type (total volume, 70%; cortex, 87% reduction). Ischemic damage compared with WT mice was not significantly altered in mice lacking either IL-1 alpha or IL-1 beta alone. IL-1 beta mRNA, but not IL-1 alpha or the IL-1 type 1 receptor, was strongly induced by MCAO in WT and IL-1 alpha KO mice.Administration (intracerebroventricularly) of recombinant IL-1 receptor antagonist significantly reduced infarct volume in WT (-32%) and IL-1 alpha KO (- 48%) mice, but had no effect on injury in IL-1 beta or IL-1 alpha/beta KO mice.These data confirm that IL-1 plays a major role in ischemic brain injury. They also show that chronic deletion of IL-1 a or IL-1 beta fails to influence brain damage, probably because of compensatory changes in the IL-1 system in IL-1 alpha KO mice and changes in IL-1-independent mediators of neuronal death in IL-1 beta KO mice.