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High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis

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Abstract

Objective

Intravenous immunoglobulin therapy has been proposed as an advanced treatment for sepsis. Yet, its benefit remains unclear and the mechanism of action is poorly understood. One key mediator in the development of sepsis is high mobility group box 1 (HMGB1). Therefore, we examined the serum and lung tissue levels of HMGB1 in a rat model of sepsis.

Design and setting

Prospective controlled animal study in a university laboratory.

Materials

Rats received either cecal ligation and puncture-induced sepsis or had additional intravenous immunoglobulin treatment in boluses of 100, 300, or 1,000 mg/kg.

Measurements and results

After induction of sepsis and respective treatment conditions, histopathology, wet/dry weight ratios, and signaling molecules were examined in pulmonary tissue. Serum and pulmonary levels of cytokine and HMGB1 were measured. High dose intravenous immunoglobulin (1,000 mg/kg)-treated animals demonstrated significantly improved survival and pulmonary histopathology compared to the control rats. Serum and pulmonary HMGB1 levels were lower over time among intravenous immunoglobulin-treated animals. Furthermore, administration of intravenous immunoglobulin resulted in inhibition of NF-κB activity.

Conclusions

High-dose intravenous immunoglobulin decreased the mortality and pulmonary pathology in a rat model of sepsis. A significant reduction in HMGB1 levels was also observed, which may be mediated by inhibition of inflammation and NF-κB.

Descriptor

23. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI): experimental models.

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Acknowledgments

The authors wish to thank Dr. Tomohisa Uchida for giving us helpful advice and for scoring lung injuries.

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Authors and Affiliations

  1. Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

    Satoshi Hagiwara, Hideo Iwasaka, Akira Hasegawa, Nobuhiko Asai & Takayuki Noguchi

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  1. Satoshi Hagiwara
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  2. Hideo Iwasaka
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  3. Akira Hasegawa
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  4. Nobuhiko Asai
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Correspondence to Satoshi Hagiwara.

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Hagiwara, S., Iwasaka, H., Hasegawa, A. et al. High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis. Intensive Care Med 34, 1812–1819 (2008). https://doi.org/10.1007/s00134-008-1161-1

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  • DOI: https://doi.org/10.1007/s00134-008-1161-1

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