Evaluation of the importance of intracellular metabolism in individual differences in drug hypersensitivity using a mouse model of cutaneous adverse drug reaction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15311
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: University of Toyama
• Principal Investigator: Susukida Takeshi 富山大学, 学術研究部薬学・和漢系, 助教 (50880689)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 薬物過敏症 / HLA / CD8陽性T細胞 / 細胞内エネルギー代謝 / 解糖系

Outline of Final Research Achievements

Drug hypersensitivity associated with specific human leukocyte antigen (HLA) allotype does not occur in all subjects of a given HLA model population, suggesting the difficulties to predict the onset risk without considering additional factors. In this study, we demonstrated that the expression level of Hk2 and glycolysis level in CD8+ T cells was upregulated in our mouse model of cutaneous adverse drug reaction. In addition, glycolysis inhibition by either glycolysis inhibitor treatment or dietary calorie restriction resulted in attenuation of drug hypersensitivity.

Free Research Field

医薬品安全性学

Academic Significance and Societal Importance of the Research Achievements

本研究によって薬物過敏症の個人差を生み出す免疫細胞内のエネルギー代謝環境の重要性が実証された。さらに、食事内容によって生体での栄養状態が異なる場合においても薬物過敏症発症の大小が決定づけられることが明らかとなり、食生活の違いが発症環境要因に位置付けられる可能性も示された。今後のさらなる研究の発展によって薬物過敏症の発症リスクの高い集団をより正確に見極められるようになることで、より安全な個別化医療の提供が実現可能となることが期待される。