Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children

Yoshinori Ito, Yuka Torii, Rieko Ohta, Masaki Imai, Shinya Hara, Yoshihiko Kawano, Tadashi Matsubayashi, Ayano Inui, Tetsushi Yoshikawa, Naoko Nishimura, Takao Ozaki, Tsuneo Morishima, Hiroshi Kimura

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: The 2009 A(H1N1) influenza virus has caused a large outbreak, and resulted in major complications of severe pneumonia and acute encephalopathy in the pediatric population in Japan. Methods: This study examined six patients with acute encephalopathy, 34 patients with severe pneumonia, five patients with both pneumonia and encephalopathy, and 46 patients without severe complications. The concentrations of 27 cytokines were examined in the cerebrospinal fluid of patients with encephalopathy, and the levels of these cytokines, Cytochrome c, high-mobility group box 1 (HMGB1) were measured in the serum of all patients. Results: Patients with severe pneumonia had higher serum concentrations of 16 cytokines, including Th1 cytokines, Th2 cytokines, chemokines, and growth factors, than patients with uncomplicated influenza. The distribution of 27 cytokines in the CSF did not parallel the serum levels in 11 patients with acute encephalopathy. HMGB1 concentrations in the serum were significantly higher in pneumonia patients with or without encephalopathy than in uncomplicated influenza patients, and were significantly associated with the upregulation of 10 cytokines. Conclusions: Elevated levels of Th2 cytokines appear to be unique to influenza caused by 2009 H1N1 influenza virus and HMGB1 could play an important role in the pathogenesis of severe pneumonia. There appear to be different pathologic processes for encephalopathy and pneumonia.

Original languageEnglish
Pages (from-to)180-187
Number of pages8
JournalCytokine
Volume56
Issue number2
DOIs
Publication statusPublished - 01-11-2011

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Brain Diseases
Human Influenza
Pneumonia
Cytokines
Viruses
H1N1 Subtype Influenza A Virus
Serum
Cerebrospinal fluid
Pediatrics
Cytochromes c
Chemokines
Intercellular Signaling Peptides and Proteins
Pathologic Processes
Orthomyxoviridae
Disease Outbreaks
Cerebrospinal Fluid
Japan
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Ito, Yoshinori ; Torii, Yuka ; Ohta, Rieko ; Imai, Masaki ; Hara, Shinya ; Kawano, Yoshihiko ; Matsubayashi, Tadashi ; Inui, Ayano ; Yoshikawa, Tetsushi ; Nishimura, Naoko ; Ozaki, Takao ; Morishima, Tsuneo ; Kimura, Hiroshi. / Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children. In: Cytokine. 2011 ; Vol. 56, No. 2. pp. 180-187.
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abstract = "Background: The 2009 A(H1N1) influenza virus has caused a large outbreak, and resulted in major complications of severe pneumonia and acute encephalopathy in the pediatric population in Japan. Methods: This study examined six patients with acute encephalopathy, 34 patients with severe pneumonia, five patients with both pneumonia and encephalopathy, and 46 patients without severe complications. The concentrations of 27 cytokines were examined in the cerebrospinal fluid of patients with encephalopathy, and the levels of these cytokines, Cytochrome c, high-mobility group box 1 (HMGB1) were measured in the serum of all patients. Results: Patients with severe pneumonia had higher serum concentrations of 16 cytokines, including Th1 cytokines, Th2 cytokines, chemokines, and growth factors, than patients with uncomplicated influenza. The distribution of 27 cytokines in the CSF did not parallel the serum levels in 11 patients with acute encephalopathy. HMGB1 concentrations in the serum were significantly higher in pneumonia patients with or without encephalopathy than in uncomplicated influenza patients, and were significantly associated with the upregulation of 10 cytokines. Conclusions: Elevated levels of Th2 cytokines appear to be unique to influenza caused by 2009 H1N1 influenza virus and HMGB1 could play an important role in the pathogenesis of severe pneumonia. There appear to be different pathologic processes for encephalopathy and pneumonia.",
author = "Yoshinori Ito and Yuka Torii and Rieko Ohta and Masaki Imai and Shinya Hara and Yoshihiko Kawano and Tadashi Matsubayashi and Ayano Inui and Tetsushi Yoshikawa and Naoko Nishimura and Takao Ozaki and Tsuneo Morishima and Hiroshi Kimura",
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Ito, Y, Torii, Y, Ohta, R, Imai, M, Hara, S, Kawano, Y, Matsubayashi, T, Inui, A, Yoshikawa, T, Nishimura, N, Ozaki, T, Morishima, T & Kimura, H 2011, 'Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children', Cytokine, vol. 56, no. 2, pp. 180-187. https://doi.org/10.1016/j.cyto.2011.07.016

Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children. / Ito, Yoshinori; Torii, Yuka; Ohta, Rieko; Imai, Masaki; Hara, Shinya; Kawano, Yoshihiko; Matsubayashi, Tadashi; Inui, Ayano; Yoshikawa, Tetsushi; Nishimura, Naoko; Ozaki, Takao; Morishima, Tsuneo; Kimura, Hiroshi.

In: Cytokine, Vol. 56, No. 2, 01.11.2011, p. 180-187.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children

AU - Ito, Yoshinori

AU - Torii, Yuka

AU - Ohta, Rieko

AU - Imai, Masaki

AU - Hara, Shinya

AU - Kawano, Yoshihiko

AU - Matsubayashi, Tadashi

AU - Inui, Ayano

AU - Yoshikawa, Tetsushi

AU - Nishimura, Naoko

AU - Ozaki, Takao

AU - Morishima, Tsuneo

AU - Kimura, Hiroshi

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Background: The 2009 A(H1N1) influenza virus has caused a large outbreak, and resulted in major complications of severe pneumonia and acute encephalopathy in the pediatric population in Japan. Methods: This study examined six patients with acute encephalopathy, 34 patients with severe pneumonia, five patients with both pneumonia and encephalopathy, and 46 patients without severe complications. The concentrations of 27 cytokines were examined in the cerebrospinal fluid of patients with encephalopathy, and the levels of these cytokines, Cytochrome c, high-mobility group box 1 (HMGB1) were measured in the serum of all patients. Results: Patients with severe pneumonia had higher serum concentrations of 16 cytokines, including Th1 cytokines, Th2 cytokines, chemokines, and growth factors, than patients with uncomplicated influenza. The distribution of 27 cytokines in the CSF did not parallel the serum levels in 11 patients with acute encephalopathy. HMGB1 concentrations in the serum were significantly higher in pneumonia patients with or without encephalopathy than in uncomplicated influenza patients, and were significantly associated with the upregulation of 10 cytokines. Conclusions: Elevated levels of Th2 cytokines appear to be unique to influenza caused by 2009 H1N1 influenza virus and HMGB1 could play an important role in the pathogenesis of severe pneumonia. There appear to be different pathologic processes for encephalopathy and pneumonia.

AB - Background: The 2009 A(H1N1) influenza virus has caused a large outbreak, and resulted in major complications of severe pneumonia and acute encephalopathy in the pediatric population in Japan. Methods: This study examined six patients with acute encephalopathy, 34 patients with severe pneumonia, five patients with both pneumonia and encephalopathy, and 46 patients without severe complications. The concentrations of 27 cytokines were examined in the cerebrospinal fluid of patients with encephalopathy, and the levels of these cytokines, Cytochrome c, high-mobility group box 1 (HMGB1) were measured in the serum of all patients. Results: Patients with severe pneumonia had higher serum concentrations of 16 cytokines, including Th1 cytokines, Th2 cytokines, chemokines, and growth factors, than patients with uncomplicated influenza. The distribution of 27 cytokines in the CSF did not parallel the serum levels in 11 patients with acute encephalopathy. HMGB1 concentrations in the serum were significantly higher in pneumonia patients with or without encephalopathy than in uncomplicated influenza patients, and were significantly associated with the upregulation of 10 cytokines. Conclusions: Elevated levels of Th2 cytokines appear to be unique to influenza caused by 2009 H1N1 influenza virus and HMGB1 could play an important role in the pathogenesis of severe pneumonia. There appear to be different pathologic processes for encephalopathy and pneumonia.

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