Recent studies show that alcohol exposure can induce glial production of neuroimmune factors in the CNS. Of these, IL-6 has gained attention because it is involved in a number of important physiological and pathophysiological processes that could be affected by alcohol-induced CNS production of IL-6, particularly under conditions of excessive alcohol use. For example, IL-6 has been shown to play a role in hippocampal behaviors and synaptic plasticity (long-term potentiation; LTP) associated with memory and learning. Surprisingly, in our in vitro studies of LTP at the Schaffer collateral to CA1 pyramidal neuron synapse in hippocampus from transgenic mice that express elevated levels of astrocyte produced IL-6 (TG), LTP was not altered by the increased levels of IL-6. However, exposure to acute alcohol revealed neuroadaptive changes that served to protect LTP against the alcohol-induced reduction of LTP observed in hippocampus from non-transgenic control mice (WT). Here we examined the induction phase of LTP to assess if presynaptic neuroadaptive changes occurred in the hippocampus of TG mice that contributed to the resistance of LTP to alcohol. Results are consistent with a role for IL-6-induced neuroadaptive effects on presynaptic mechanisms involved in transmitter release in the resistance of LTP to alcohol in hippocampus from the TG mice. These actions are important with respect to a role for IL-6 in physiological and pathophysiological processes in the CNS and in CNS actions of alcohol, especially when excessive alcohol used is comorbid with conditions associated with elevated levels of IL-6 in the CNS.

最近的研究表明，酒精暴露可以诱导中枢神经系统中神经免疫因子的神经胶质细胞产生。其中，IL-6 之所以受到关注，是因为它参与了许多重要的生理和病理生理过程，这些过程可能会受到酒精诱导的中枢神经系统产生 IL-6 的影响，尤其是在过度饮酒的情况下。例如，IL-6 已被证明在与记忆和学习相关的海马行为和突触可塑性（长期增强；LTP）中发挥作用。令人惊讶的是，在我们对表达升高水平的星形胶质细胞产生的 IL-6 (TG) 的转基因小鼠的海马 CA1 锥体神经元突触的 Schaffer 侧枝 LTP 的体外研究中，LTP 并未因 IL-6 水平升高而改变。然而，暴露于急性酒精揭示了神经适应性变化，这些变化有助于保护 LTP 免受在非转基因对照小鼠 (WT) 的海马中观察到的酒精诱导的 LTP 减少。在这里，我们检查了 LTP 的诱导阶段，以评估 TG 小鼠的海马中是否发生突触前神经适应变化，这有助于 LTP 对酒精的抵抗。结果与 IL-6 诱导的神经适应作用对 TG 小鼠海马 LTP 对酒精的抵抗中涉及递质释放的突触前机制的作用一致。这些作用对于 IL-6 在 CNS 的生理和病理生理过程以及酒精的 CNS 作用中的作用很重要，特别是当使用过量酒精与与 CNS 中 IL-6 水平升高相关的病症时。