title: Etanercept reduces neuroinflammation and lethality in mouse model of Japanese encephalitis.
abstract: BACKGROUND
  Japanese encephalitis virus (JEV) is a neurotropic flavivirus that causes Japanese encephalitis (JE), which leads to high fatality rates in human. Tumor necrosis factor alpha (TNF-α) is a key factor that mediates immunopathology in the central nervous system (CNS) during JE. Etanercept is a safe anti-TNF-α drug that has been commonly used in the treatment of various human autoimmune diseases.
  
  
  METHODS
  The effect of etanercept on JE was investigated with a JEV-infected mouse model. Four groups of mice were assigned to receive injections of phosphate-buffered saline, etanercept, JEV, or JEV plus etanercept. Inflammatory responses in mouse brains and mortality of mice were evaluated within 23 days post infection.
  
  
  RESULTS
  The in vitro assay with mouse neuron/glia cultures showed that etanercept treatment reduced the inflammatory response induced by JEV infection. In vivo experiments further demonstrated that administration of etanercept protected mice from JEV-induced lethality. Neuronal damage, glial activation, and secretion of proinflammatory cytokines were found to be markedly decreased in JEV-infected mice that received etanercept treatment. Additionally, etanercept treatment restored the integrity of the blood-brain barrier and reduced viral load in mouse brains.
  
  
  CONCLUSIONS
  Etanercept effectively reduces the inflammation and provides protection against acute encephalitis in a JEV-infected mouse model.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Bibo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Leqiang
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Yueyun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Ali
authors.initials: A
authors.lastname: Zohaib
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Xindi
authors.initials: X
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Wen
authors.initials: W
authors.lastname: He
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Cao
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000378:metabolism; D004672:Encephalitis, Japanese / Q000188:drug therapy* / Q000473:pathology; D000068800:Etanercept; D007074:Immunoglobulin G / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
keywords: Japanese encephalitis virus; TNF-α; etanercept; inflammation; viral encephalitis