Effect of anesthetics on sepsis-induced cerebral inflammatory cytokine upregulagtion

Research Project

Project/Area Number	25462432
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Anesthesiology
Research Institution	Kyoto University
Principal Investigator	Tanaka Tomoharu 京都大学, 医学(系)研究科(研究院), 助教 (10402893)
Co-Investigator(Renkei-kenkyūsha)	HIROTA Kiichi 関西医科大学, 医学部, 准教授 (00283606)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000) Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	マイクログリア / IL-1b / 麻酔薬 / 炎症性サイトカイン / マイクリグリア / IL-1
Outline of Final Research Achievements	General anesthetics including isoflurane and propofol time-and dose-dependently suppressed inflammatory cytokine, especially IL-1b, upregulation induced by LPS in microglia cell line. Both anesthetics significantly suppressed the phosphorylation of MAPK, and the result suggested that the effect of anesthetics on MAPK is the essential mechanism of cytokine suppression. In the experiment adopting sepsis model mice, isoflurane significantly suppressed IL-1b induction in brain, and decreased ACTH concentration in blood. Those results suggested that general anesthetics affect the sepsis-induced IL-1b induction in brain, and may have a great impact on stress response using hypothalamus-adrenal gland axis.