The effect for C-reactive protein (CRP) for sever sepsis

• Project/Area Number: 16K11424
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Nippon Medical School
• Principal Investigator: YOKOMURO Shigeki 日本医科大学, 医学部, 准教授 (30267223)
• Co-Investigator(Kenkyū-buntansha): 松田 明久 日本医科大学, 医学部, 助教 (00366741) ; 宮下 正夫 日本医科大学, 医学部, 教授 (70229847) ; 山田 真吏奈 日本医科大学, 医学部, 講師 (70508621) ; 木下 学 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 免疫・微生物学, 准教授 (70531391)
• Research Collaborator: SEKIGUCHI Kumiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 敗血症 / C-reactive protein (CRP) / 感染症

Outline of Final Research Achievements

C-reactive protein (CRP), named from its capacity to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae, is well known as an acute-phase protein. Synthetic CRP has been recently developed and it was revealed that CRP is closely involved in the innate immunity system. Synthetic CRP treatment stimulates macrophages to phagocytize microbes. This project goal is to test the CRP treatment experts protective effects in sepsis. Sepsis was induced by cecum ligation and puncture (CLP) in male C57BL/6J under anesthesia. CRP (250, 500ug/mouse/day, IP) was initiated after CLP. As a result of that CRP dose-dependently improved survival of septic male C57BL/6J. Although CRP effect for survival of sepsis mouse model, plasma level of IL6 and TNF were not reduced compared with CLP. And then, we did not obvious the protective effect of CRP is due to reduction in bacteria.

Academic Significance and Societal Importance of the Research Achievements

これまで重症敗血症診療において集中治療管理技術の進歩や新規抗菌薬開発が一定の効果を上げてきたことは自明である。しかし，急速な高齢化に伴う罹患率の上昇，依然として高い致死率を勘案すると，今後，さらなる社会問題となることは間違いない。侵襲学において，多彩な生理活性を有する血清蛋白であるCRPに着目した本研究は，これまでになく学術的に極めて独創的である。本研究の成果は，重症敗血症の炎症性生体反応メカニズムの解明においてブレイクスルーとなる可能性があり，将来的に臨床応用により在院期間短縮，医療費削減などへの寄与が期待される。