Regulation of IL-18, IL-38 and complements for the treatment of inflammatory pulmonary diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08637
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kurume University
• Principal Investigator: Hoshino Tomoaki 久留米大学, 医学部, 教授 (00261066)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 炎症 / IL-38

Outline of Final Research Achievements

Interleukin (IL)-38 was discovered in 2001 and is a member of the IL-1 family of cytokines. IL-38 shows anti-inflammatory activity in several inflammatory diseases. We reported that IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction. We demonstrated that high IL-38 expression in tumor cells was significantly associated with reduction of CD8(+) TILs and tumor progression. These results suggest that IL-38 could be a therapeutic target for lung cancer. The IL-38 mRNA and protein expression were enhanced in the active mucosa of ulcerative colitis (UC), but not in Crohn's disease. DSS-colitis was significantly exacerbated in IL-38KO mice compared to wild type mice. IL-38 may play an anti-inflammatory and protective role in the pathophysiology of IBD, in particular ulcerative colitis, through the suppression of IL-36-induced inflammatory responses.

Free Research Field

内科

Academic Significance and Societal Importance of the Research Achievements

喘息、癌、炎症性腸疾患の克服は大きな課題である。。本研究では、これら疾患におけるサイトカインIL-38と炎症の制御を研究した。マウス喘息モデル、坦がん(tumor bearing)モデルとDextran sulfate sodium(DSS)で誘導した炎症性腸疾患モデルでサイトカインIL-38は炎症を制御することを示した。サイトカインの制御は喘息、癌、炎症性腸疾患の治療に応用できると考えられた。