Approach to treatment of decubitus ulcer by IL-33 inhibition

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08661
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Mayuim Komine 自治医科大学, 医学部, 教授 (00282632)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 褥瘡 / 虚血再灌流 / IL-33 / 核内因子 / 中和抗体 / 治療

Outline of Final Research Achievements

We made decubitus ulcer model utilizing ischemia-reperfusion model in IL-33KO and WT mice. IL-33KO mice showed remarkable suppression of ulcer formation compared to WT mice. Thus we tried to utilize neutralization antibody for suppression of decubitus ulcer formation in mice.Anti-IL-33 antibody and anti-ST2L antibody partially suppressed the formation of decubitus ulcer formation in WT mice.IL-33 has been reported to suppress structural proteins, such as filaggrin and keratins. We assumed that IL-33 exerted its effects, not only as cytokine, but also as nuclear protein to suppress keratin-related proteins in our mice model.
Above these facts suggested that neutralization of soluble IL-33 cytokine or its receptor may suppress partially decubitus ulcer formation, but may not suppress completely.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

褥瘡はすでに形成された潰瘍に対する治療は存在するが、圧力を受けたあとの早期段階での治療は存在しない。早期の褥瘡に対する治療薬の開発ができれば、圧負荷後から潰瘍形成に至る期間に潰瘍形成を抑制する治療が可能となり、臨床的に有意義であると考えたが、今回の検討結果からは、サイトカインとしてのIL-33を抑制するのみでは、褥瘡形成の予防は難しいと考えられた。核内のIL-33まで発現抑制するか、あるいはIL-1などの別のターゲットについても検討する必要があると考えている。