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

Identifieur interne : 001A40 ( Ncbi/Checkpoint ); précédent : 001A39; suivant : 001A41

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

Auteurs : Nobuyuki Nosaka [Japon] ; Masato Yashiro [Japon] ; Mutsuko Yamada [Japon] ; Yosuke Fujii [Japon] ; Hirokazu Tsukahara [Japon] ; Keyue Liu [Japon] ; Masahiro Nishibori [Japon] ; Akihiro Matsukawa [Japon] ; Tsuneo Morishima [Japon]

Source :

RBID : PMC:4490661

Descripteurs français

English descriptors

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.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0983-9) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1186/s13054-015-0983-9
PubMed: 26067826
PubMed Central: 4490661


Affiliations:


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PMC:4490661

Le document en format XML

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<sec>
<title>Introduction</title>
<p id="Par1">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.</p>
</sec>
<sec>
<title>Methods</title>
<p id="Par2">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.</p>
</sec>
<sec>
<title>Results</title>
<p id="Par3">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,
<italic>p</italic>
 < 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.</p>
</sec>
<sec>
<title>Conclusions</title>
<p id="Par4">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.</p>
</sec>
<sec>
<title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s13054-015-0983-9) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<name sortKey="Nosaka, Nobuyuki" sort="Nosaka, Nobuyuki" uniqKey="Nosaka N" first="Nobuyuki" last="Nosaka">Nobuyuki Nosaka</name>
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<name sortKey="Fujii, Yosuke" sort="Fujii, Yosuke" uniqKey="Fujii Y" first="Yosuke" last="Fujii">Yosuke Fujii</name>
<name sortKey="Liu, Keyue" sort="Liu, Keyue" uniqKey="Liu K" first="Keyue" last="Liu">Keyue Liu</name>
<name sortKey="Matsukawa, Akihiro" sort="Matsukawa, Akihiro" uniqKey="Matsukawa A" first="Akihiro" last="Matsukawa">Akihiro Matsukawa</name>
<name sortKey="Morishima, Tsuneo" sort="Morishima, Tsuneo" uniqKey="Morishima T" first="Tsuneo" last="Morishima">Tsuneo Morishima</name>
<name sortKey="Nishibori, Masahiro" sort="Nishibori, Masahiro" uniqKey="Nishibori M" first="Masahiro" last="Nishibori">Masahiro Nishibori</name>
<name sortKey="Tsukahara, Hirokazu" sort="Tsukahara, Hirokazu" uniqKey="Tsukahara H" first="Hirokazu" last="Tsukahara">Hirokazu Tsukahara</name>
<name sortKey="Yamada, Mutsuko" sort="Yamada, Mutsuko" uniqKey="Yamada M" first="Mutsuko" last="Yamada">Mutsuko Yamada</name>
<name sortKey="Yashiro, Masato" sort="Yashiro, Masato" uniqKey="Yashiro M" first="Masato" last="Yashiro">Masato Yashiro</name>
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</tree>
</affiliations>
</record>

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