Neuroimmune factors, including the cytokine interleukin-6 (IL-6), are important chemical regulators of central nervous system (CNS) function under both physiological and pathological conditions. Elevated expression of IL-6 occurs in the CNS in a variety of disorders associated with altered CNS function, including excessive alcohol use. Alcohol-induced production of IL-6 has been reported for several CNS regions including the cerebellum. Cerebellar actions of alcohol occur through a variety of mechanisms, but alcohol-induced changes in signal transduction, transcription, and translation are known to play important roles. IL-6 is an activator of signal transduction that regulates gene expression. Thus, alcohol-induced IL-6 production could contribute to cerebellar effects of alcohol by altering gene expression, especially under conditions of chronic alcohol abuse, where IL-6 levels could be habitually elevated. To gain an understanding of the effects of alcohol on IL-6 signal transduction, we studied activation/expression of IL-6 signal transduction partners STAT3 (Signal Transducer and Activator of Transcription), CCAAT-enhancer binding protein (C/EBP) beta, and p42/p44 mitogen-activated protein kinase (MAPK) at the protein level. Cerebella of transgenic mice that express elevated levels of astrocyte produced IL-6 in the CNS were studied. Results show that the both IL-6 and chronic intermittent alcohol exposure/withdrawal affect IL-6 signal transduction partners and that the actions of IL-6 and alcohol interact to alter activation/expression of IL-6 signal transduction partners. The alcohol/IL-6 interactions may contribute to cerebellar actions of alcohol, whereas the effects of IL-6 alone may have relevance to cerebellar changes occurring in CNS disorders associated with elevated levels of IL-6.

中文翻译：

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酒精改变转基因小鼠中枢神经系统中的 IL-6 信号转导，增加星形胶质细胞的 IL-6 表达。


神经免疫因子，包括细胞因子白细胞介素-6 (IL-6)，是生理和病理条件下中枢神经系统 (CNS) 功能的重要化学调节剂。在多种与 CNS 功能改变相关的疾病（包括过量饮酒）中，CNS 中 IL-6 的表达升高。据报道，包括小脑在内的几个中枢神经系统区域酒精诱导产生 IL-6。酒精对小脑的作用有多种机制，但已知酒精引起的信号转导、转录和翻译变化发挥着重要作用。 IL-6 是调节基因表达的信号转导激活剂。因此，酒精诱导的 IL-6 产生可能通过改变基因表达来促进酒精对小脑的影响，特别是在长期酗酒的情况下，IL-6 水平可能会习惯性升高。为了了解酒精对 IL-6 信号转导的影响，我们研究了 IL-6 信号转导伙伴 STAT3（信号转导子和转录激活子）、CCAAT 增强子结合蛋白 (C/EBP) beta 的激活/表达，以及蛋白质水平上的 p42/p44 丝裂原激活蛋白激酶 (MAPK)。研究人员对中枢神经系统中星形胶质细胞表达水平升高的转基因小鼠小脑产生的 IL-6 进行了研究。结果表明，IL-6 和慢性间歇性酒精暴露/戒断都会影响 IL-6 信号转导伙伴，并且 IL-6 和酒精的作用相互作用，改变 IL-6 信号转导伙伴的激活/表达。 酒精/IL-6 相互作用可能有助于酒精的小脑作用，而单独的 IL-6 的作用可能与 IL-6 水平升高相关的中枢神经系统疾病中发生的小脑变化有关。