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  • Title: Etanercept reduces neuroinflammation and lethality in mouse model of Japanese encephalitis.
    Author: Ye J, Jiang R, Cui M, Zhu B, Sun L, Wang Y, Zohaib A, Dong Q, Ruan X, Song Y, He W, Chen H, Cao S.
    Journal: J Infect Dis; 2014 Sep 15; 210(6):875-89. PubMed ID: 24652493.
    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.
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