Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis
Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis
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DOI：
10.1007/s00540-018-2548-y
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发表时间：
2018-08
影响因子：
2.8
通讯作者：
S. Maeda;T. Andoh;Rieko Onishi;Y. Tomoyasu;H. Higuchi;T. Miyawaki
中科院分区：
文献类型：
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作者：
S. Maeda;T. Andoh;Rieko Onishi;Y. Tomoyasu;H. Higuchi;T. Miyawaki
目的神经元炎症是由全身性炎症引起的认知功能障碍。IL-6在神经元炎症和认知功能障碍的治疗中发挥着至关重要的作用。瑞芬太尼是一种超短效阿片类药物，可控制外周的炎症反应，但不能控制大脑。因此，雷米芬太尼在神经组织中的抗炎作用和cAMP在这些effects的参与进行了调查在本study.MethodsMice分为4组：对照组，雷米芬太尼，LPS，LPS +雷米芬太尼。检测4组大鼠脑组织中促炎细胞因子mRNA水平及血清皮质酮、儿茶酚胺和IL-6水平。通过免疫染色验证了注射LPS后小鼠脑中IL-6和星形胶质细胞的共定位。LPS和/或雷米芬太尼诱导的变化，在培养的神经胶质细胞的细胞内cAMP水平的测定，和cAMP对LPS诱导的IL-6 mRNA的表达水平的影响进行了评估。ResultsRemifentanil抑制IL-6 mRNA水平在小鼠脑中的增加，也抑制血浆IL-6，皮质酮，和去甲肾上腺素在炎症状态下的反应。在下丘脑，IL-6定位于正中隆起，GFAP免疫反应性被特异性检测。在培养的细胞中，雷米芬太尼抑制IL-6 mRNA水平和细胞内cAMP水平的增加后，管理的LPS，这增强了IL-6 mRNA的表达在响应LPS.ConclusionRemifentanil抑制IL-6 mRNA水平的增加，在大脑中的炎症状态，这种效果可能是由于其直接作用于神经细胞通过抑制细胞内cAMP，而不是皮质酮。
PurposeNeuronal inflammation is caused by systemic inflammation and induces cognitive dysfunction. IL-6 plays a crucial role in therapies for neuronal inflammation and cognitive dysfunction. Remifentanil, an ultra-short-acting opioid, controls inflammatory reactions in the periphery, but not in the brain. Therefore, the anti-inflammatory effects of remifentanil in neuronal tissue and the involvement of cAMP in these effects were investigated in the present study.MethodsMice were divided into 4 groups: control, remifentanil, LPS, and LPS + remifentanil. Brain levels of pro-inflammatory cytokine mRNA, and serum levels of corticosterone, catecholamine and IL-6 were measured in the 4 groups. The co-localization of IL-6 and astrocytes in the mouse brain after the LPS injection was validated by immunostaining. LPS and/or remifentanil-induced changes in intracellular cAMP levels in cultured glial cells were measured, and the effects of cAMP on LPS-induced IL-6 mRNA expression levels were evaluated.ResultsRemifentanil suppressed increase in IL-6 mRNA levels in the mouse brain, and also inhibited the responses of plasma IL-6, corticosterone, and noradrenaline in an inflammatory state. In the hypothalamus, IL-6 was localized in the median eminence, at which GFAP immunoreactivity was specifically detected. In cultured cells, remifentanil suppressed increase in IL-6 mRNA levels and intracellular cAMP levels after the administration of LPS, and this enhanced IL-6 mRNA expression in response to LPS.ConclusionRemifentanil suppressed increase in IL-6 mRNA levels in the brain in an inflammatory state, and this effect may be attributed to its direct action on neuronal cells through the inhibition of intracellular cAMP rather than corticosterone.