Elucidation of mechanism and effect of hypothermia during sepsis on granulopoiesis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Hiroshima University
• Principal Investigator: SHIME NOBUAKI 広島大学, 医系科学研究科(医), 教授 (00260795)
• Co-Investigator(Kenkyū-buntansha): 平位 秀世 京都大学, 医学研究科, 助教 (50315933)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 好中球 / 分化 / 低体温 / 敗血症

Outline of Final Research Achievements

We investigated the effect and mechanism of hypothermia associated with sepsis on host defense. In a mouse model exposed to the cold environment, the number of peripheral blood neutrophils and the number of mature neutrophils in bone marrow cells were decreased, while the number of cells in the intermediate stage between mature neutrophils and progenitor cells was increased. This was also comfirmed in the hypothermic culture model of whole bone marrow cells, and the number of neutrophils that went toward differentiation and maturation from neutrophil progenitor cells was significantly reduced. In the mouse sepsis model, the number of peripheral blood neutrophils was significantly reduced in individuals who had decreased body temperature. Effect of decreased level of aspartic acid on neutrophil differentiation was suspected using metabolome analysis. The adjusted mortality rate was significantly higher in patients with severe infections with a body temperature below 36 degrees.

Free Research Field

集中治療医学、救急医学、感染症学

Academic Significance and Societal Importance of the Research Achievements

敗血症は致死率の高い重症感染病態であるが、敗血症時において併発する低体温が生体防御能に及ぼす影響とその機序については明らかではなかった。感染防御の最前線で働くのは好中球である。低体温時における好中球の分化増殖に及ぼす影響を、生体防御能の観点より検討することは、病態生理の解明のみならず、これに立脚した新しい治療戦略を確立するための基礎的知見を提供しうる。