Balschun D, Wetzel W, Del Rey A, Pitossi F, Schneider H, Zuschratter W, Besedovsky H O
Leibniz Institute for Neurobiology, Magdeburg, Germany.
FASEB J. 2004 Nov;18(14):1788-90. doi: 10.1096/fj.04-1625fje. Epub 2004 Sep 2.
It is known that proinflammatory cytokines such as interleukin-6 (IL-6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL-6 in the "healthy" brain in synaptic plasticity and memory consolidation. During long-term potentiation (LTP) in vitro and in freely moving rats, IL-6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N-methyl-D-aspartate receptors with (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Blockade of endogenous IL-6 by application of a neutralizing anti-IL-6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL-6, 90 min after hippocampus-dependent spatial alternation learning resulted in a significant improvement of long-term memory. In view of the suggested role of LTP in memory formation, these data implicate IL-6 in the mechanisms controlling the kinetics and amount of information storage.
众所周知，诸如白细胞介素-6（IL-6）等促炎细胞因子在疾病状态下会在中枢神经系统（CNS）中表达，并影响包括记忆和学习在内的多种脑功能。与在病理条件下观察到的这些效应相反，在此我们描述了IL-6在“健康”大脑中对突触可塑性和记忆巩固的生理功能。在体外长期增强（LTP）期间以及在自由活动的大鼠中，海马体中的IL-6基因表达显著增加。这种增加是持久的，对增强具有特异性，并且可通过用（+/-）-2-氨基-5-膦酰戊酸（AP-5）抑制N-甲基-D-天冬氨酸受体来阻止。在破伤风后90分钟应用中和性抗IL-6抗体阻断内源性IL-6会导致LTP显著延长。同样，在海马体依赖性空间交替学习后90分钟阻断内源性IL-6会导致长期记忆显著改善。鉴于LTP在记忆形成中的假定作用，这些数据表明IL-6参与了控制信息存储的动力学和量的机制。
