Construction of improved lymphocyte transformation test based on the onset and aggravation mechanism of drug-induced liver injury

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670068
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Chiba University
• Principal Investigator: ITO Kousei 千葉大学, 薬学研究科(研究院), 教授 (30323405)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: HLA / 薬剤性肝障害 / リンパ球幼弱化試験

Outline of Final Research Achievements

Drug hypersensitivity reaction is one of the categories of drug-induced liver injury (DILI). However, current clinical test such as lymphocyte transformation test (LTT) could not detect all the causative drugs with hypersensitivity reaction because the assay does not include hepatocytes that metabolize drugs and subsequently propose antigens to the lymphocytes. To overcome that shortcoming, it is needed to add hepatocytes that are endowed with metabolic enzyme activity and antigen presentation. We firstly constructed transgenic mice constitutively expressing human HLA molecule related to some kinds of DILI. In addition, adenoviruses carrying HLA to transiently express its product in mouse primary hepatocytes were constructed. It is expected that the sensitivity of current LTT assay is improved by using these novel hepatocytes tools.

Free Research Field

毒性学