Mechanism and therapy for immune suppression caused by severe infection and / or surgery.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02896
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: UCHIDA KANJI 東京大学, 医学部附属病院, 教授 (60302709)
• Co-Investigator(Kenkyū-buntansha): 山田 芳嗣 国際医療福祉大学, 国際医療福祉大学三田病院, 教授 (30166748) ; 比留間 孝広 東京大学, 医学部附属病院, 助教 (40572277)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 敗血症 / 重症感染症 / 手術侵襲 / 免疫抑制 / 免疫賦活

Outline of Final Research Achievements

A mouse model of human septic peritonitis was created and the function of innate immune cells in the lungs and abdominal cavity was observed. In the model of moderate severity (about 10% mortality), the function of alveolar macrophages in the lungs was found to be suppressed, with reduced maturation marker expression, even on day 4, where mice were in the recovery period. Impaired function and maturity were restored by systemic IFNβ administration or transtracheal GM-CSF administration. In the severe sepsis model, abdominal phagocyte function was greatly reduced as well and was restored by systemic IFNβ administration. However, this effect was not seen when prophylactic administration was given before sepsis.

Free Research Field

麻酔科学・集中治療医学

Academic Significance and Societal Importance of the Research Achievements

敗血症は、いまだに死亡率が高く、確立された薬物療法が無い病態である。臨床試験で有効性が示せない理由の１つに、病態の不均一性が挙げられている。本研究は、動物モデルで、ヒトの腹膜炎敗血症の病態を再現し、一次免疫担当細胞の機能が抑制されていることを直接的に示したこと、また免疫賦活効果を示すサイトカインを投与し、実際に機能の復活と生存率の改善を観察できたことは、今後の治療につながる社会的意義が大きい成果であると考える。