Basic research for elucidation of the mechanism of multi-organ immune dysfunction in the lack of enteral nutrition

• Project/Area Number: 16K11395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: The University of Tokyo
• Principal Investigator: MURAKOSHI Satoshi 東京大学, 医学部附属病院, 講師 (10647407)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 静脈栄養 / 腸管免疫 / 肝免疫 / サイトカイン / 肝単核球 / クッパー細胞 / 腸管リンパ装置 / 経腸栄養 / 接着分子 / GALT / 栄養学

Outline of Final Research Achievements

We performed the basic study to elucidate the mechanism of intestinal and hepatic immunodeficiency in the lack of enteral nutrition with mouse nutrition management model.
As a result of the examination, it was suggested that the intestinal immunodeficiency was caused by changes in the number of lymphocytes of the gut-associated lymphoid tissue and changes in the intestinal cytokine environment. It was also suggested that the hepatic immunodeficiency was due to the functional changes of hepatic mononuclear cells.

Academic Significance and Societal Importance of the Research Achievements

栄養療法は患者管理の基盤である。生理的な栄養管理法である経腸（経口）栄養が不可能な場合、栄養管理は完全静脈栄養に依存するが感染性合併症の発生率上昇や予後の悪化をまねく。その原因として腸管を中心とした粘膜免疫だけではなく、肝臓の免疫も低下する多臓器免疫不全の惹起が指摘されている。しかし、その機序は複雑で不明な点が多く、有効な対策法の開発を難しくしている。
本研究では経腸栄養欠如による腸管や肝免疫の低下機序について検討しその要因を明らかにできた。この結果は、経腸栄養が欠如しても腸管免疫や肝免疫の維持が可能となる栄養管理法開発につながり、重症患者の栄養管理技術の向上に寄与することが期待される。

Research Products

• [Presentation] 感染予防に役立栄養の力～投与ルートからみたそのパワーの考察～ (2020)
  • Author(s): 村越智
  • Organizer: 第35回日本臨床栄養代謝学会学術集会
• [Presentation] Influences of aging on expression of lipopolysaccharide receptor of Kupffer cells in mice (2018)
  • Author(s): Satoshi Murakoshi
  • Organizer: ESPEN CONGRESS 2018
  • Int'l Joint Research
• [Presentation] Influences of aging on Monocyte chemoattractant protein-1 (MCP-1) production of hepatic mononuclear cells in mice (2018)
  • Author(s): Satoshi Murakoshi
  • Organizer: ASPEN 2018 Nutrition Science & Practice Conference
  • Int'l Joint Research
• [Presentation] Influences of aging on the phagocytic activity of Kupffer cells in mice (2017)
  • Author(s): Satoshi Murakoshi
  • Organizer: ESPEN CONGRESS 2017
  • Int'l Joint Research
• [Presentation] 栄養投与ルートの相違が侵襲時の肝単核球機能におよぼす影響 (2016)
  • Author(s): 村越智
  • Organizer: JDDW 2016
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2016-11-03
• [Presentation] Influences of nutritional route on Kupffer cell phagocytic function (2016)
  • Author(s): Satoshi Murakoshi
  • Organizer: ESPEN CONGRESS 2016
  • Place of Presentation: Copenhagen, DENMARK
  • Year and Date: 2016-09-17
  • Int'l Joint Research