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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09595
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kurume University
• Principal Investigator: Hoshino Tomoaki 久留米大学, 医学部, 教授 (00261066)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: IL-38 / 喘息 / 好酸球 / IL-5

Outline of Final Research Achievements

The role of IL-38, a new member of the IL-1 family, in airway eosinophilic inflammatory conditions such as asthma is unclear. To investigate the role of IL-38 in airway eosinophilic inflammation, an IL-38-gene deficient (KO) murine asthma model was analyzed. The IL-38 and IL-5 mRNA in WT mice was significantly higher after OVA challenge than after saline challenge (p<0.05). The number of airway eosinophils in IL-38-KO mice was significantly lower than in WT mice after OVA challenge (p<0.01). BALF analysis confirmed the lower number of airway eosinophils in IL-38-KO mice and showed that this was significantly associated with lower IL-5 protein levels (r=0.92, p<0.0001). However, the additional rm IL-38 protein did not neutralize airway eosinophilia in IL-38-KO mice.IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction.We also reported that IL-18 strongly involves in activation of Macrophage Activation Syndrome（MAS).

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

新規IL-1ファミリーサイトカインIL-38は抗炎症性サイトカインの可能性があることが示唆された（Biochemistry and Biophysics Reports 2015）。一方、IL-38は炎症性サイトカインの可能性を本研究で証明した。すなわち、IL-38は抗炎症性と炎症性サイトカインの二つの可能性を本研究で証明した。
申請者は抗ヒトIL-38モノクロナール抗体を樹立した。抗IL-38モノクロナール抗体H127CはBiolegend, eBioscienceから世界中で販売され,IL-38の研究に役立っている。