title: General anesthetics inhibit LPS-induced IL-1β expression in glial cells.
abstract: BACKGROUND
  Glial cells, including microglia and astrocytes, are considered the primary source of proinflammatory cytokines in the brain. Immune insults stimulate glial cells to secrete proinflammatory cytokines that modulate the acute systemic response, which includes fever, behavioral changes, and hypothalamic-pituitary-adrenal (HPA) axis activation. We investigated the effect of general anesthetics on proinflammatory cytokine expression in the primary cultured glial cells, the microglial cell line BV-2, the astrocytic cell line A-1 and mouse brain.
  
  
  RESULTS
  Primary cultured glial cells were exposed to lipopolysaccharide (LPS) in combination with general anesthetics including isoflurane, pentobarbital, midazolam, ketamine, and propofol. Following this treatment, we examined glial cell expression of the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α). LPS-induced expression of IL-1β mRNA and protein were significantly reduced by all the anesthetics tested, whereas IL-6 and TNF-α mRNA expression was unaffected. The anesthetics suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation, but did not affect nuclear factor-kappaB and activator protein-1 activation. The same effect was observed with BV-2, but not with A-1 cells. In the mouse experiments, LPS was injected intraperitoneally, and isoflurane suppressed IL-1β in the brain and adrenocorticotropic hormone in plasma, but not IL-1β in plasma.
  
  
  CONCLUSIONS
  Taken together, our results indicate that general anesthetics inhibit LPS-induced IL-1β upregulation in glial cells, particularly microglia, and affects HPA axis participation in the stress response.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kai
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: Department of Anesthesia, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Anesthesiology, Kansai Medical University, Hirakata, Japan.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Hirota
mesh_terms: D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018681:Anesthetics, General; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D048052:Mitogen-Activated Protein Kinase 3