Pre-exposure to volatile anesthetics inhibits inflammation induced by various stimuli, including surgical procedures and ischemia. We hypothesize that volatile anesthetics may induce anti-inflammatory effects via a mechanism involving regulation of histone deacetylases (HDACs). Pre-exposure of 1.5% isoflurane for 0.5 h induced anti-inflammatory effects [measured by cytokine production of tumor necrosis factor-ɑ, interleukin-8 (IL-8) and IL-1β] in both human THP-1 cells and primary human peripheral blood monocytes stimulated by lipopolysaccharide. In human THP-1 cells, coadministration of the HDAC inhibitor trichostatin A (TSA) blocked the isoflurane-induced anti-inflammatory effects. TSA also blocked isoflurane-upregulated HDAC1-3 expression and isoflurane-reduced nuclear translocation of p65 and p50 subunits of nuclear factor-κB (NF-κB). The ability of isoflurane to reduce NF-κB nuclear translocation and proinflammatory responses in the cell line was blocked by gene silencing of HDAC1 and HDAC2, but not by gene silencing of HDAC3. A coimmunoprecipitation assay demonstrated that the decreased interaction between HDAC1 and HDAC2 through lipopolysaccharide was restored by isoflurane pretreatment. These findings were validated in primary human peripheral blood monocytes wherein gene silencing of HDAC1 and HDAC2 resulted in increased cytokine production and NF-κB nuclear translocation induced by isoflurane pre-exposure and lipopolysaccharide stimulation. These results indicate that anti-inflammatory effects of the volatile anesthetic isoflurane in human monocytes involve regulation of HDAC1 and HDAC2.

中文翻译：

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HDAC1和HDAC2调节人单核细胞中麻醉异氟烷的抗炎作用。

预暴露于挥发性麻醉剂会抑制各种刺激（包括手术程序和局部缺血）引起的炎症。我们假设挥发性麻醉药可能通过涉及调节组蛋白脱乙酰基酶（HDACs）的机制诱导抗炎作用。在人类THP-1细胞和原代人类中，预先暴露1.5％的异氟烷​​0.5 h诱导的抗炎作用[通过肿瘤坏死因子-α，白介素8（IL-8）和IL-1β的细胞因子产生来测量]脂多糖刺激外周血单核细胞。在人类THP-1细胞中，HDAC抑制剂曲古抑菌素A（TSA）的共同给药可阻断异氟烷诱导的抗炎作用。TSA还阻断了异氟烷上调的HDAC1-3表达，并减少了异氟烷减少的核因子-κB（NF-κB）p65和p50亚基的核易位。HDAC1和HDAC2的基因沉默阻止了异氟烷减少细胞系中NF-κB核易位和促炎反应的能力，但HDAC3的基因沉默却没有阻止。免疫沉淀试验表明，异氟烷预处理可恢复通过脂多糖引起的HDAC1和HDAC2之间相互作用的降低。这些发现在原代人外周血单核细胞中得到了验证，其中，HDAC1和HDAC2的基因沉默导致异氟烷预暴露和脂多糖刺激导致细胞因子生成增加和NF-κB核易位。这些结果表明，挥发性麻醉剂异氟烷在人单核细胞中的抗炎作用涉及HDAC1和HDAC2的调节。