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Critical Care
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice

Authors: Nobuyuki Nosaka, Masato Yashiro, Mutsuko Yamada, Yosuke Fujii, Hirokazu Tsukahara, Keyue Liu, Masahiro Nishibori, Akihiro Matsukawa, Tsuneo Morishima

Published in: Critical Care | Issue 1/2015

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Abstract

Introduction

Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice.

Methods

Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation.

Results

Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment.

Conclusions

Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.
Appendix
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Metadata
Title
Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice
Authors
Nobuyuki Nosaka
Masato Yashiro
Mutsuko Yamada
Yosuke Fujii
Hirokazu Tsukahara
Keyue Liu
Masahiro Nishibori
Akihiro Matsukawa
Tsuneo Morishima
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-0983-9

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