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Anti‐high mobility group box‐1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide
Author(s) -
Nosaka Nobuyuki,
Hatayama Kazuki,
Yamada Mutsuko,
Fujii Yousuke,
Yashiro Masato,
Wake Hidenori,
Tsukahara Hirokazu,
Nishibori Masahiro,
Morishima Tsuneo
Publication year - 2018
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.25076
Subject(s) - hmgb1 , medicine , encephalopathy , lipopolysaccharide , monoclonal antibody , edema , influenza a virus , virus , immunology , virology , inflammation , antibody
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.