title: Isoflurane and sevoflurane increase interleukin-6 levels through the nuclear factor-kappa B pathway in neuroglioma cells.
abstract: BACKGROUND
  Isoflurane can increase pro-inflammatory cytokine interleukin (IL)-6 levels. However, the up-stream mechanism remains unknown. Nuclear factor-kappa B (NF-κB) promotes the generation of pro-inflammatory cytokines. We examined the effects of isoflurane and sevoflurane on the NF-κB signalling pathway and its association with IL-6 levels in cultured cells.
  
  
  METHODS
  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-κB. Pyrrolidine dithiocarbamate (an NF-κB inhibitor) or 2-deoxy-d-glucose (2-DG) (an inhibitor of glucose glycolysis) was applied 1 h before anaesthetic treatment.
  
  
  RESULTS
  Isoflurane or sevoflurane treatment increased the levels of IL-6 [isoflurane: 410% (54); sevoflurane: 290% (24)], the nuclear levels of NF-κB [isoflurane: 170% (36); sevoflurane: 320% (30)], and the transcription activity of NF-κB in H4 cells. Moreover, isoflurane enhanced the transcription activity of NF-κB in mouse microglia, but not primary neurones. Finally, pyrrolidine dithiocarbamate and 2-DG attenuated isoflurane-induced increases in IL-6 and NF-κB, and the transcription activity of NF-κB.
  
  
  CONCLUSIONS
  These studies in H4 cells suggest that the NF-κB signalling pathway could contribute to isoflurane or sevoflurane-induced neuroinflammation. This could lead to the targeted intervention of anaesthetic-induced neuroinflammation.
authors.affiliation: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Dong
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
mesh_terms: D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D005910:Glioma; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007530:Isoflurane / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D018685:Anesthetics, Inhalation; D000963:Antimetabolites; D018836:Inflammation Mediators; D015850:Interleukin-6; D008738:Methyl Ethers; D016328:NF-kappa B; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D000077149:Sevoflurane; D011392:Proline; D003847:Deoxyglucose; D007530:Isoflurane
keywords: NF-κB; anaesthetic; interleukin-6