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Anti-High Mobility Group Box-1 Monoclonal Antibody Treatment of Brain Edema Induced by Influenza Infection and Lipopolysaccharide

tetano

Editor, Senior Moderator
J Med Virol. 2018 Mar 24. doi: 10.1002/jmv.25076. [Epub ahead of print]
[h=1]Anti-High Mobility Group Box-1 Monoclonal Antibody Treatment of Brain Edema Induced by Influenza Infection and Lipopolysaccharide.[/h] Nosaka N[SUP]1[/SUP], Hatayama K[SUP]1[/SUP], Yamada M[SUP]1[/SUP], Fujii Y[SUP]1[/SUP], Yashiro M[SUP]1[/SUP], Wake H[SUP]2[/SUP], Tsukahara H[SUP]1[/SUP], Nishibori M[SUP]2[/SUP], Morishima T[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Encephalopathy is a major cause of influenza-associated child death and severe neurological sequelae in Japan, highlighting the urgent need for new therapeutic strategies. In this study, we evaluated the effects of anti-high mobility group box-1 monoclonal antibody (α-HMGB1) treatment on brain edema induced by influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice. The results showed that administration of 7.5 mg/kg α-HMGB1 1 h after IAV (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also observed suppression of oxidative stress and different cytokines in IAV-inoculated mice. The expression of plasminogen activator inhibitor-1 was also attenuated following treatment with α-HMGB1. Notably, α-HMGB1 treatment had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment may improve the prognosis in cases with influenza-associated encephalopathy by attenuating brain edema and reducing the inflammatory responses induced by HMGB1. This article is protected by copyright. All rights reserved.


[h=4]KEYWORDS:[/h] brain edema; encephalopathy; high mobility group box-1; influenza virus; monoclonal antibody

PMID: 29573352 DOI: 10.1002/jmv.25076
 
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