Understanding of the molecular mechanism for pharmacokinetic alteration caused by pro-inflammatory cytokines

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Okayama University (2017-2019); Tohoku University (2016)
• Principal Investigator: Kodama Susumu 岡山大学, 医歯薬学総合研究科, 准教授 (20621460)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 薬物動態 / 炎症性サイトカイン / 遺伝子発現調節

Outline of Final Research Achievements

Under pathological conditions associated with inflammation, the expression of drug-metabolizing enzymes and transporters that regulate drug response is markedly down-regulated. However, details of the mechanism underlying their down-regulation are still unknown. In this study, we have investigated the molecular mechanisms by which pro-inflammatory cytokine IL-6 regulates human CYP1A2 and CAR expression, utilizing in vitro system. Our results show that the IL-6 responsive transcription factor DEC1 could act as a common repressor on their promoters.

Free Research Field

衛生薬学

Academic Significance and Societal Importance of the Research Achievements

様々な生体側の要因が薬物動態に影響与えることが知られている。本研究では、炎症を伴う病態時に炎症性サイトカインによって引き起こされる薬物動態の変動機構の一端を明らかにした。さらに近年、免疫系に作用するバイオ医薬品の開発・普及が進む中、それらの従来の低分子医薬品との相互作用リスク回避の観点において、有用な情報を提供すると考える。