敗血症時のAutophagyと栄養管理
Autophagyは, 細胞の自己成分をlysosomeに運び込み分解する機構であり, 必ずしも細胞死を意味するわけではない. 飢餓応答としての栄養供給という働き以外にも, 不要なオルガネラの分解, 病原微生物の排除, 腫瘍抑制などの役割も確認されており, むしろ生命維持に必須のシステムである. そして敗血症病態下での重要臓器 (肝, 腎, 脾臓の免疫担当細胞など) においては, 発症早期には一過性にautophagyは亢進するものの, その後停滞傾向に向かうことが判明してきており, 臓器保護的な役割を担っている. 一方, 敗血症時の骨格筋では, autophagy過活性が筋萎縮を惹起すること...
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| Published in | 外科と代謝・栄養 Vol. 53; no. 6; pp. 287 - 292 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本外科代謝栄養学会
15.12.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0389-5564 2187-5154 |
| DOI | 10.11638/jssmn.53.6_287 |
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| Abstract | Autophagyは, 細胞の自己成分をlysosomeに運び込み分解する機構であり, 必ずしも細胞死を意味するわけではない. 飢餓応答としての栄養供給という働き以外にも, 不要なオルガネラの分解, 病原微生物の排除, 腫瘍抑制などの役割も確認されており, むしろ生命維持に必須のシステムである. そして敗血症病態下での重要臓器 (肝, 腎, 脾臓の免疫担当細胞など) においては, 発症早期には一過性にautophagyは亢進するものの, その後停滞傾向に向かうことが判明してきており, 臓器保護的な役割を担っている. 一方, 敗血症時の骨格筋では, autophagy過活性が筋萎縮を惹起することも報告され, 臓器やその構成細胞によっては諸刃の剣である. 敗血症とautophagyの関与の解明と, autophagyの生体でのモニタリング手法の確立が, 敗血症時のautophagy動態の制御を企図した栄養管理実現へのポイントである. |
|---|---|
| AbstractList | Autophagyは, 細胞の自己成分をlysosomeに運び込み分解する機構であり, 必ずしも細胞死を意味するわけではない. 飢餓応答としての栄養供給という働き以外にも, 不要なオルガネラの分解, 病原微生物の排除, 腫瘍抑制などの役割も確認されており, むしろ生命維持に必須のシステムである. そして敗血症病態下での重要臓器 (肝, 腎, 脾臓の免疫担当細胞など) においては, 発症早期には一過性にautophagyは亢進するものの, その後停滞傾向に向かうことが判明してきており, 臓器保護的な役割を担っている. 一方, 敗血症時の骨格筋では, autophagy過活性が筋萎縮を惹起することも報告され, 臓器やその構成細胞によっては諸刃の剣である. 敗血症とautophagyの関与の解明と, autophagyの生体でのモニタリング手法の確立が, 敗血症時のautophagy動態の制御を企図した栄養管理実現へのポイントである. |
| Author | 渡邉, 栄三 |
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| DOI | 10.11638/jssmn.53.6_287 |
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| References | 26) van den Berghe G, Wouters P, Weekers F et al.: Intensive insulin therapy in critically ill patients. N Engl J Med 345: 1359‐1367, 2001 11) Watanabe E, Nishida O, Kakihana Y et al.: Pharmacokinetics, Pharmacodynamics and Safety of Nivolumab in Patients With Sepsis‐induced immunosuppression : A multicenter, open‐label phase 1/2 study. Shock: 2019 13) Takahashi W, Watanabe E, Fujimura L et al.: Kinetics and protective role of autophagy in a mouse cecal ligation and puncture‐induced sepsis. Crit Care 17: R160, 2013 18) Muscaritoli M, Anker SD, Argiles J et al.: Consensus definition of sarcopenia, cachexia and pre‐cachexia : joint document elaborated by Special Interest Groups（SIG） “cachexia‐anorexia in chronic wasting diseases” and “nutrition in geriatrics” . Clin Nutr 29: 154‐159, 2010 22) Nishida O, Ogura H, Egi M et al.: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016). Acute Med Surg 5: 3‐89, 2018 12) Mizushima N, Levine B, Cuervo AM et al.: Autophagy fights disease through cellular self‐digestion. Nature 451: 1069‐1075, 2008 3) 渡邉栄三: AutophagyとMitophagy. 外科と代謝・栄養50: 307‐311, 2016 7) 日本集中治療医学会重症患者の栄養管理ガイドライン作成委員会: 日本版重症患者の栄養療法ガイドライン. 日集中医誌23 :185‐281, 2016 20) Vassilakopoulos T, Petrof BJ: Ventilator‐induced diaphragmatic dysfunction. Am J Respir Crit Care Med 169: 336‐341, 2004 24) Watanabe E, Oami T, Sunahara S et al.: Programmed Cell Death in Sepsis‐Identification of Friend or Foe‐. Chiba Medical J 92E: 15‐24, 2016 9) Watanabe E, Thampy LK, Hotchkiss RS: Immunoadjuvant therapy in sepsis : novel strategies for immunosuppressive sepsis coming down the pike. Acute Med Surg 5: 309‐315, 2018 23) Casaer MP, Mesotten D, Hermans G et al.: Early versus late parenteral nutrition in critically ill adults. N Engl J Med 365: 506‐517, 2011 16) Oami T, Watanabe E, Hatano M et al.: Blocking Liver Autophagy Accelerates Apoptosis and Mitochondrial Injury in Hepatocytes and Reduces Time to Mortality in a Murine Sepsis Model. Shock 50: 427‐434, 2018 27) Arabi YM, Aldawood AS, Haddad SH et al.: Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N Engl J Med 372: 2398‐2408, 2015 19) Pasiakos SM, McClung JP: Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids. Nutr Rev 69: 550‐557, 2011 2) 渡邉栄三, 大網毅彦, 砂原聡ほか: 外科侵襲とAutophagy‐敗血症, がんからPICS (persistent inflammation, immunosuppression, catabolism syndrome) まで−. 外科と代謝・栄養51: 9‐15, 2017 15) Watanabe E, Muenzer JT, Hawkins WG et al.: Sepsis induces extensive autophagic vacuolization in hepatocytes : a clinical and laboratory‐based study. Lab Invest 89: 549‐561, 2009 4) Hotchkiss RS, Strasser A, McDunn JE et al.: Cell death. N Engl J Med 361: 1570‐1583, 2009 5) Ho J, Yu J, Wong SH et al.: Autophagy in sepsis: Degradation into exhaustion? Autophagy 12: 1073‐1082, 2016 10) Hotchkiss RS, Colston E, Yende S et al.: Immune checkpoint inhibition in sepsis : a Phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab. Intensive Care Med 45: 1360‐1371, 2019 6) Taylor BE, McClave SA, Martindale RG et al.: Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient : Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). Crit Care Med 44: 390‐438, 2016 28) 寺島秀夫, 米山智: 侵襲下の血糖値と感染防御能 ～Tight Glycemic Controlのみで十分なのか～. 外科と代謝・栄養45: 199‐210, 2011 25) Seok J, Warren HS, Cuenca AG et al.: Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 110: 3507‐3512, 2013 21) Hussain SN, Mofarrahi M, Sigala I et al.: Mechanical ventilation‐induced diaphragm disuse in humans triggers autophagy. Am J Respir Crit Care Med 182: 1377‐1386, 2010 1) Kuma A, Hatano M, Matsui M et al.: The role of autophagy during the early neonatal starvation period. Nature 432: 1032‐1036, 2004 14) Sunahara S, Watanabe E, Hatano M et al.: Influence of autophagy on acute kidney injury in a murine cecal ligation and puncture sepsis model. Sci Rep 8: 1050, 2018 8) Hotchkiss RS, Swanson PE, Freeman BD et al.: Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 27: 1230‐1251, 1999 17) Oami T, Watanabe E, Hatano M et al.: Suppression of T Cell Autophagy Results in Decreased Viability and Function of T Cells Through Accelerated Apoptosis in a Murine Sepsis Model. Crit Care Med 45: e77‐e85, 2017 |
| References_xml | – reference: 21) Hussain SN, Mofarrahi M, Sigala I et al.: Mechanical ventilation‐induced diaphragm disuse in humans triggers autophagy. Am J Respir Crit Care Med 182: 1377‐1386, 2010 – reference: 11) Watanabe E, Nishida O, Kakihana Y et al.: Pharmacokinetics, Pharmacodynamics and Safety of Nivolumab in Patients With Sepsis‐induced immunosuppression : A multicenter, open‐label phase 1/2 study. Shock: 2019 – reference: 8) Hotchkiss RS, Swanson PE, Freeman BD et al.: Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 27: 1230‐1251, 1999 – reference: 5) Ho J, Yu J, Wong SH et al.: Autophagy in sepsis: Degradation into exhaustion? Autophagy 12: 1073‐1082, 2016 – reference: 28) 寺島秀夫, 米山智: 侵襲下の血糖値と感染防御能 ～Tight Glycemic Controlのみで十分なのか～. 外科と代謝・栄養45: 199‐210, 2011 – reference: 16) Oami T, Watanabe E, Hatano M et al.: Blocking Liver Autophagy Accelerates Apoptosis and Mitochondrial Injury in Hepatocytes and Reduces Time to Mortality in a Murine Sepsis Model. Shock 50: 427‐434, 2018 – reference: 25) Seok J, Warren HS, Cuenca AG et al.: Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 110: 3507‐3512, 2013 – reference: 3) 渡邉栄三: AutophagyとMitophagy. 外科と代謝・栄養50: 307‐311, 2016 – reference: 22) Nishida O, Ogura H, Egi M et al.: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016). Acute Med Surg 5: 3‐89, 2018 – reference: 1) Kuma A, Hatano M, Matsui M et al.: The role of autophagy during the early neonatal starvation period. Nature 432: 1032‐1036, 2004 – reference: 15) Watanabe E, Muenzer JT, Hawkins WG et al.: Sepsis induces extensive autophagic vacuolization in hepatocytes : a clinical and laboratory‐based study. Lab Invest 89: 549‐561, 2009 – reference: 9) Watanabe E, Thampy LK, Hotchkiss RS: Immunoadjuvant therapy in sepsis : novel strategies for immunosuppressive sepsis coming down the pike. Acute Med Surg 5: 309‐315, 2018 – reference: 19) Pasiakos SM, McClung JP: Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids. Nutr Rev 69: 550‐557, 2011 – reference: 27) Arabi YM, Aldawood AS, Haddad SH et al.: Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N Engl J Med 372: 2398‐2408, 2015 – reference: 18) Muscaritoli M, Anker SD, Argiles J et al.: Consensus definition of sarcopenia, cachexia and pre‐cachexia : joint document elaborated by Special Interest Groups（SIG） “cachexia‐anorexia in chronic wasting diseases” and “nutrition in geriatrics” . Clin Nutr 29: 154‐159, 2010 – reference: 23) Casaer MP, Mesotten D, Hermans G et al.: Early versus late parenteral nutrition in critically ill adults. N Engl J Med 365: 506‐517, 2011 – reference: 2) 渡邉栄三, 大網毅彦, 砂原聡ほか: 外科侵襲とAutophagy‐敗血症, がんからPICS (persistent inflammation, immunosuppression, catabolism syndrome) まで−. 外科と代謝・栄養51: 9‐15, 2017 – reference: 4) Hotchkiss RS, Strasser A, McDunn JE et al.: Cell death. N Engl J Med 361: 1570‐1583, 2009 – reference: 7) 日本集中治療医学会重症患者の栄養管理ガイドライン作成委員会: 日本版重症患者の栄養療法ガイドライン. 日集中医誌23 :185‐281, 2016 – reference: 17) Oami T, Watanabe E, Hatano M et al.: Suppression of T Cell Autophagy Results in Decreased Viability and Function of T Cells Through Accelerated Apoptosis in a Murine Sepsis Model. Crit Care Med 45: e77‐e85, 2017 – reference: 6) Taylor BE, McClave SA, Martindale RG et al.: Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient : Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). Crit Care Med 44: 390‐438, 2016 – reference: 26) van den Berghe G, Wouters P, Weekers F et al.: Intensive insulin therapy in critically ill patients. N Engl J Med 345: 1359‐1367, 2001 – reference: 12) Mizushima N, Levine B, Cuervo AM et al.: Autophagy fights disease through cellular self‐digestion. Nature 451: 1069‐1075, 2008 – reference: 10) Hotchkiss RS, Colston E, Yende S et al.: Immune checkpoint inhibition in sepsis : a Phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab. Intensive Care Med 45: 1360‐1371, 2019 – reference: 24) Watanabe E, Oami T, Sunahara S et al.: Programmed Cell Death in Sepsis‐Identification of Friend or Foe‐. Chiba Medical J 92E: 15‐24, 2016 – reference: 13) Takahashi W, Watanabe E, Fujimura L et al.: Kinetics and protective role of autophagy in a mouse cecal ligation and puncture‐induced sepsis. Crit Care 17: R160, 2013 – reference: 14) Sunahara S, Watanabe E, Hatano M et al.: Influence of autophagy on acute kidney injury in a murine cecal ligation and puncture sepsis model. Sci Rep 8: 1050, 2018 – reference: 20) Vassilakopoulos T, Petrof BJ: Ventilator‐induced diaphragmatic dysfunction. Am J Respir Crit Care Med 169: 336‐341, 2004 |
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| Snippet | Autophagyは, 細胞の自己成分をlysosomeに運び込み分解する機構であり, 必ずしも細胞死を意味するわけではない. 飢餓応答としての栄養供給という働き以外にも, 不要なオルガネラの分解, 病原微生物の排除, 腫瘍抑制などの役割も確認されており, むしろ生命維持に必須のシステムである.... Autophagyは, 細胞の自己成分をlysosomeに運び込み分解する機構であり, 必ずしも細胞死を意味するわけではない. 飢餓応答としての栄養供給という働き以外にも, 不要なオルガネラの分解. 病原微生物の排除, 腫瘍抑制などの役割も確認されており, むしろ生命維持に必須のシステムである.... |
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| SubjectTerms | apoptosis permissive underfeeding メタボロミクス 免疫麻痺 細胞死 |
| Title | 敗血症時のAutophagyと栄養管理 |
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