Isoflurane can increase pro-inflammatory cytokine interleukin (IL)-6 levels. However, the up-stream mechanism remains unknown. Nuclear factor-kappa B (NF-B) promotes the generation of pro-inflammatory cytokines. We examined the effects of isoflurane and sevoflurane on the NF-B signalling pathway and its association with IL-6 levels in cultured cells. H4 human neuroglioma cells (H4 cells), and mouse primary neurones and microglia were treated with 2 isoflurane or 4.1 sevoflurane for 6 h, for analysis of IL-6 and NF-B. Pyrrolidine dithiocarbamate (an NF-B inhibitor) or 2-deoxy-d-glucose (2-DG) (an inhibitor of glucose glycolysis) was applied 1 h before anaesthetic treatment. Isoflurane or sevoflurane treatment increased the levels of IL-6 [isoflurane: 410 (54); sevoflurane: 290 (24)], the nuclear levels of NF-B [isoflurane: 170 (36); sevoflurane: 320 (30)], and the transcription activity of NF-B in H4 cells. Moreover, isoflurane enhanced the transcription activity of NF-B in mouse microglia, but not primary neurones. Finally, pyrrolidine dithiocarbamate and 2-DG attenuated isoflurane-induced increases in IL-6 and NF-B, and the transcription activity of NF-B. These studies in H4 cells suggest that the NF-B signalling pathway could contribute to isoflurane or sevoflurane-induced neuroinflammation. This could lead to the targeted intervention of anaesthetic-induced neuroinflammation.
基金:
National Institutes of Health, Bethesda, MD, USA [R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, IL, USA; Cure Alzheimer's Fund, Wellesley, MA, USA
第一作者单位:[1]Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA[2]Harvard Univ, Sch Med, Charlestown, MA 02129 USA[3]Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Anesthesiol, Shanghai 200011, Peoples R China
通讯作者:
通讯机构:[1]Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA[2]Harvard Univ, Sch Med, Charlestown, MA 02129 USA
推荐引用方式(GB/T 7714):
Zhang L.,Zhang J.,Yang L.,et al.Isoflurane and sevoflurane increase interleukin-6 levels through the nuclear factor-kappa B pathway in neuroglioma cells[J].BRITISH JOURNAL OF ANAESTHESIA.2013,110:82-91.doi:10.1093/bja/aet115.
APA:
Zhang, L.,Zhang, J.,Yang, L.,Dong, Y.,Zhang, Y.&Xie, Z..(2013).Isoflurane and sevoflurane increase interleukin-6 levels through the nuclear factor-kappa B pathway in neuroglioma cells.BRITISH JOURNAL OF ANAESTHESIA,110,
MLA:
Zhang, L.,et al."Isoflurane and sevoflurane increase interleukin-6 levels through the nuclear factor-kappa B pathway in neuroglioma cells".BRITISH JOURNAL OF ANAESTHESIA 110.(2013):82-91