Immunopharmacological-efficacy analysis of vitamin K2 for the purpose of introduction for immunosuppressive therapy in renal transplantation.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Sugiyama Kentaro 東京薬科大学, 薬学部, 准教授 (50574745)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 腎移植患者 / ビタミンK2 / 適応外使用

Outline of Final Research Achievements

Vitamin K2 significantly inhibited proliferation of concanavarin A-stimulated peripheral blood mononuclear cells (PBMCs) derived from dialysis patients and healthy subjects. The vitamin K2 potencies were similar in these subjects. VK2 did not largely change the amounts of cytokines produced from activated PBMCs of both dialysis patients and healthy subjects. Percentage of regulatory T cells in PBMCs of dialysis patients, but not of healthy subjects, decreased by VK2 treatment.
Renal transplant recipients are received combination immunosuppressive therapy with steroids. Deviation in the VK2 pharmacological efficacies was small in PBMCs of both healthy subjects and dialysis patients. However, the steroid potencies on the activated PBMCs deviated largely. Therefore, we also developed and evaluated the PBMC suppressive efficacy of VK2 combined with other immunosuppressive drugs, aiming the application of this strategy to a new combination immunosuppressive therapy.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

腎移植における免疫抑制療法は、過剰免疫抑制による日和見感染症やステロイド性の骨粗鬆症等の副作用も散見される。VK2は、透析患者と健常者のいずれのPBMCに対しても増殖抑制効果を示した。その薬効には個人差が少なく、両群のPBMCに対し同等な薬効が得られた。VK2は骨粗鬆症に適応を持ち副作用が少ない。そのため従来の免疫抑制療法にVK2を加えた薬物療法は、免疫抑制薬の減量による副作用軽減とステロイド性骨粗鬆症の軽減に大きく寄与出来ると考えられる。さらに、VK2と他の免疫抑制薬の併用を模した薬効評価系を確立することにより、VK2を併用した腎移植免疫抑制薬物療法の個別化に大きく貢献するものと思われた。