Study of cytokine storm using the silkworm model

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15461
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Teikyo University
• Principal Investigator: Miyashita Atsushi 帝京大学, 付置研究所, 講師 (40818308)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 自然免疫 / サイトカインストーム / カイコ / 炎症性疾患 / ショック / 敗血症 / 細菌 / 緑膿菌

Outline of Final Research Achievements

In this study, we were able to construct a systemic inflammation model in silkworms that leads to death within a few hours due to a "cytokine storm," by administering heat-killed Pseudomonas aeruginosa and Staphylococcus aureus into their bloodstream. Particularly, the severity of the symptoms increased when these heat-killed bacteria were co-administered with organic solvents such as dimethyl sulfoxide, or when the silkworms used in the experiments were subjected to starvation stress. Improvements in symptoms were observed with the use of nafamostat (a protease inhibitor) and steroids (anti-inflammatory drugs), which are used in human clinical settings. This allows us to establish a foundation for using this model to explore compounds that may have clinical applications in humans.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果によって、これまで不明点が多く残されていた全身性・急性の炎症性ショック反応の進行メカニズムを研究するための基盤を提供することができた。特に、ヒトの臨床で一定の症状改善効果が得られているナファモスタットやステロイド等の薬剤がカイコモデルでも治療効果を示したことから、ヒトへの外挿性が期待できるモデルとして今後の新規治療薬スクリーニングへの応用が期待される。将来的には本モデルを用いてサイトカインストームを含む炎症性疾患に対する創薬を加速し、感染症に苦しむ人々の健康に貢献できると考えられる。