Mechanism and treatment of severe sepsis

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K17043
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Hiruma Takahiro 東京大学, 医学部附属病院, 講師 (40572277)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 敗血症 / 免疫抑制 / 腹膜炎 / 虚血再灌流傷害 / 免疫調整

Outline of Final Research Achievements

Assuming sepsis due to nosocomial pneumonia after peritonitis, we investigated the effect of interferon β administration on a two-hit animal model that causes Pseudomonas aeruginosa pneumonia after cecal ligation and puncture. Peritonitis made pneumonia more severe, and interferon β showed a therapeutic effect. In addition, the phagocytic ability of alveolar macrophages before pneumonia was evaluated, and peritonitis reduced the phagocytic ability, and interferon β restored the phagocytic ability. In addition, assuming ischemia-reperfusion due to shock or surgery, the survival rate and multi-organ damage of an animal model of intestinal ischemia-reperfusion injury were evaluated as the first hit. It was confirmed that the prolongation of the ischemic time made the disease more severe and that multiple organ damage was caused by intestinal ischemia-reperfusion.

Free Research Field

集中治療医学

Academic Significance and Societal Importance of the Research Achievements

臨床では腹膜炎、肺炎などそれ自体であれば軽症であっても、それが組み合わさることで敗血症がより重症化することは多い。本検討ではそのような状況を想定したtwo hit動物モデルに対して、その重症化のメカニズムと治療薬としてインターフェロンβの効果を検討することで、敗血症の病態把握につながる結果としての意義がある。また同様に虚血再還流による多臓器障害やその免疫機能に与える影響を検討することで、その後の侵襲による重症化に与える影響を検討することは同じく敗血症の重症化のメカニズム解析につながる。