Etanercept Reduces Neuroinflammation and Lethality in Mouse Model of Japanese Encephalitis

Abstract Background. Japanese encephalitis virus (JEV) is a neurotropic flavivirus. It causes Japanese encephalitis (JE) leading to high fatality in human. Tumor necrosis factor-alpha (TNF-α) is one of the key factors that mediate immunopathology in the central nervous system (CNS) during Japanese encephalitis. Etanercept is a safe anti-TNF-α drug which has been commonly used for the treatment of various human autoimmune diseases. Methods. The effect of etanercept on JE was investigated with JEV-infected mouse model. Four groups of mice were assigned to receive injections of PBS, etanercept, JEV and JEV plus etanercept, respectively. Inflammatory responses in mouse brains and mortality of mice were evaluated within 23 days post infection. Results. In vitro assay with mouse neuron/glia cultures showed that etanercept treatment reduced the inflammatory response induced by JEV infection. In vivo experiments further demonstrate 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 with etanercept treatment. Additionally, etanercept treatment restored the intergrity of blood brain barrier and reduced viral load in mouse brains.