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J Infect Dis. 2014 Sep 15;210(6):875-89. doi: 10.1093/infdis/jiu179. Epub 2014 Mar 20.

Etanercept reduces neuroinflammation and lethality in mouse model of Japanese encephalitis.

Author information

1
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, P.R China.

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.

KEYWORDS:

Japanese encephalitis virus; TNF-α; etanercept; inflammation; viral encephalitis

PMID:
24652493
DOI:
10.1093/infdis/jiu179
[Indexed for MEDLINE]
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