High-dose immunoglobulin preparations improve survival in a CLP-induced rat model of sepsis

Takahisa Yoshikawa, Hiroya Takeuchi, Koichi Suda, Taku Miyasho, Shingo Yamada, Minoru Okamoto, Yoshio Kawamura, Ikuro Maruyama, Masaki Kitajima, Yuukou Kitagawa

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: The efficacy of intravenous immunoglobulin G in the treatment of patients with severe sepsis or septic shock is still being debated. We investigated the impact of high-dose immunoglobulin administration on the survival rate and serum high-mobility group box chromosomal protein 1 (HMGB1) level in a rat model of sepsis created by cecal ligation and puncture (CLP). Methods: Rats received either CLP-induced sepsis or had additional immunoglobulin treatment in 1,500 or 300 mg/kg. After induction of sepsis and respective treatment conditions, pulmonary and renal tissues were examined histologically for pathological changes at postoperative hour (POH) 4, and serum cytokine and HMGB1 levels were measured at POH 4, 8, 20, and 44. Using other rats, we also observed the survival rate after CLP for 7 days. Results: Treatment with immunoglobulin significantly improved survival rate at postoperative day 7 (73% in the high-dose group vs. 33% in the control group; p=0.037). The serum lactate dehydrogenase, endotoxin, creatinine, and blood urea nitrogen levels were significantly lower in the high-dose group than in the other groups. The serum HMGB1 level had increased at 4 h postoperatively in the control group (10.2±3.3 ng/mL) and low-dose group (10.3±4.0 ng/mL), but it was significantly reduced in the high-dose group (4.2±0.8 ng/mL) compared with the control group (p=0.03). Conclusions: Our results suggest that high-dose immunoglobulin therapy may improve the serum endotoxin and HMGB1 levels and overall survival rate in sepsis by inhibiting the inflammation.

Original languageEnglish
Pages (from-to)457-465
Number of pages9
JournalLangenbeck's Archives of Surgery
Volume397
Issue number3
DOIs
Publication statusPublished - 2012 Mar

Fingerprint

High Mobility Group Proteins
HMGB1 Protein
Punctures
Ligation
Immunoglobulins
Sepsis
Survival
Serum
Survival Rate
Endotoxins
Control Groups
Passive Immunization
Blood Urea Nitrogen
Intravenous Immunoglobulins
Therapeutics
Septic Shock
L-Lactate Dehydrogenase
Creatinine
Immunoglobulin G
Cytokines

Keywords

  • Cecal ligation and puncture model
  • Endotoxin
  • HMGB1
  • Immunoglobulin
  • Sepsis

ASJC Scopus subject areas

  • Surgery

Cite this

High-dose immunoglobulin preparations improve survival in a CLP-induced rat model of sepsis. / Yoshikawa, Takahisa; Takeuchi, Hiroya; Suda, Koichi; Miyasho, Taku; Yamada, Shingo; Okamoto, Minoru; Kawamura, Yoshio; Maruyama, Ikuro; Kitajima, Masaki; Kitagawa, Yuukou.

In: Langenbeck's Archives of Surgery, Vol. 397, No. 3, 03.2012, p. 457-465.

Research output: Contribution to journalArticle

Yoshikawa, T, Takeuchi, H, Suda, K, Miyasho, T, Yamada, S, Okamoto, M, Kawamura, Y, Maruyama, I, Kitajima, M & Kitagawa, Y 2012, 'High-dose immunoglobulin preparations improve survival in a CLP-induced rat model of sepsis', Langenbeck's Archives of Surgery, vol. 397, no. 3, pp. 457-465. https://doi.org/10.1007/s00423-011-0878-4
Yoshikawa, Takahisa ; Takeuchi, Hiroya ; Suda, Koichi ; Miyasho, Taku ; Yamada, Shingo ; Okamoto, Minoru ; Kawamura, Yoshio ; Maruyama, Ikuro ; Kitajima, Masaki ; Kitagawa, Yuukou. / High-dose immunoglobulin preparations improve survival in a CLP-induced rat model of sepsis. In: Langenbeck's Archives of Surgery. 2012 ; Vol. 397, No. 3. pp. 457-465.
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AU - Okamoto, Minoru

AU - Kawamura, Yoshio

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AU - Kitagawa, Yuukou

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N2 - Purpose: The efficacy of intravenous immunoglobulin G in the treatment of patients with severe sepsis or septic shock is still being debated. We investigated the impact of high-dose immunoglobulin administration on the survival rate and serum high-mobility group box chromosomal protein 1 (HMGB1) level in a rat model of sepsis created by cecal ligation and puncture (CLP). Methods: Rats received either CLP-induced sepsis or had additional immunoglobulin treatment in 1,500 or 300 mg/kg. After induction of sepsis and respective treatment conditions, pulmonary and renal tissues were examined histologically for pathological changes at postoperative hour (POH) 4, and serum cytokine and HMGB1 levels were measured at POH 4, 8, 20, and 44. Using other rats, we also observed the survival rate after CLP for 7 days. Results: Treatment with immunoglobulin significantly improved survival rate at postoperative day 7 (73% in the high-dose group vs. 33% in the control group; p=0.037). The serum lactate dehydrogenase, endotoxin, creatinine, and blood urea nitrogen levels were significantly lower in the high-dose group than in the other groups. The serum HMGB1 level had increased at 4 h postoperatively in the control group (10.2±3.3 ng/mL) and low-dose group (10.3±4.0 ng/mL), but it was significantly reduced in the high-dose group (4.2±0.8 ng/mL) compared with the control group (p=0.03). Conclusions: Our results suggest that high-dose immunoglobulin therapy may improve the serum endotoxin and HMGB1 levels and overall survival rate in sepsis by inhibiting the inflammation.

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