Anti-high mobility group box-1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide

Nobuyuki Nosaka, Kazuki Hatayama, Mutsuko Yamada, Yosuke Fujii, Masato Yashiro, Hidenori Wake, Hirokazu Tsukahara, Masahiro Nishibori, Tsuneo Morishima

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13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1192-1198
Number of pages7
JournalJournal of Medical Virology
Issue number7
Publication statusPublished - Jul 2018


  • brain edema
  • encephalopathy
  • high mobility group box-1
  • influenza virus
  • monoclonal antibody

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases


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