Study on the pathogenesis of severe influenza virus infection associated with cytokine storm and its effective treatment options

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05348
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: The University of Tokushima
• Principal Investigator: KIDO Hiroshi 徳島大学, 先端酵素学研究所(デザイン), 特任教授 (50144978)
• Co-Investigator(Kenkyū-buntansha): 高橋 悦久 徳島大学, 先端酵素学研究所(デザイン), 特任助教 (10380065)
• Research Collaborator: SAWAFUCHI Takako ; IL INDALAO
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 感染症 / インフルエンザ / サイトカイン / ミトコンドリア / 糖代謝 / 脂質代謝 / 多臓器不全 / 血管内皮細胞

Outline of Final Research Achievements

The pathogenesis of severe influenza virus infection is associated with “influenza─cytokine─protease” cycle and “cytokine─metabolic disorder” cycle. Among the proinflammatory cytokines, IL-1β plays a key role in suppression of mitochondrial energy metabolism, cellular functions and immunological responses of host defense. We found that inhibitor of pyruvate dehydrogenase kinase 4 in glucose metabolism and bezafibrate, stimulator of lipid metabolism, in mitochondria are effective treatment options for influenza-induced metabolic disorder in mitochondria. In addition, macrolide antibiotics and the L. bulgaricus OLL1073R-1 yogurt cultures have immune-stimulator functions as adjuvants and restored antibody production rates effectively. In this project, we clarified that these drugs and materials are useful treatment options for severe influenza virus infection and multiple organ failure.

Free Research Field

病態医科学

Academic Significance and Societal Importance of the Research Achievements

人類は、新型インフルエンザや、高病原性鳥インフルエンザのパンデミックに備える必要がある。現在これらのウイルス病原体側の研究は進んでいるが、感染時の重症化する基礎疾患を持っヒトに対する重症化対策が遅れている。本研究では、インフルエンザ感染重症化の機序の詳細を明らかにし、その機序に基づく治療薬を具体的に提案しているところに学術的意義と社会的意義がある。