Anti-high mobility group box-1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide
| Autor: | Yousuke Fujii, Masato Yashiro, Kazuki Hatayama, Masahiro Nishibori, Hirokazu Tsukahara, Mutsuko Yamada, Hidenori Wake, Nobuyuki Nosaka, Tsuneo Morishima |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Lipopolysaccharide Encephalopathy chemical and pharmacologic phenomena Brain Edema medicine.disease_cause HMGB1 Virus 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Japan Orthomyxoviridae Infections Virology Influenza A virus medicine Animals Immunologic Factors HMGB1 Protein Evans Blue Mice Inbred BALB C biology business.industry Antibodies Monoclonal medicine.disease Disease Models Animal 030104 developmental biology Infectious Diseases Treatment Outcome chemistry Immunology biology.protein Female business Plasminogen activator 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Journal of medical virology. 90(7) |
| ISSN: | 1096-9071 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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