Therapeutic effect of alveolar macrophage-specific anti-IGF-1 antibody for idiopathic pulmonary fibrosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09634
• 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: Tokyo National Hospital (Clinical research)
• Principal Investigator: Ohta Ken 独立行政法人国立病院機構東京病院(臨床研究部), 臨床研究部, 名誉院長 (30160500)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: IGF-1 / 肺線維芽細胞 / マクロファージ / 特発性肺線維症

Outline of Final Research Achievements

The aim of this study was to clarify the effect(s) of pulmonary macrophage-origin IGF-1 on normal human lung fibroblasts (NHLF). First, methods were established to differentiate macrophages from human peripheral blood-derived monocytes as well as U937 cells. The macrophages derived from both monocytes and U937 cells produced IGF-1. We also established methods for co-culturing those macrophages with NHLF and for culturing NHLF in the supernatants of cultures of those macrophages. When the macrophages were co-cultured with NHLFs in the presence of anti-IGF-1–neutralizing antibody or linsitinib, an inhibitor of IGF-1 receptor, inflammatory cytokines in the supernatants of both culture systems were significantly suppressed. This study revealed that IGF-1 derived from macrophages acts via the IGF-1 receptor to induce cytokine production by NHLFs.

Free Research Field

呼吸器内科、間質性肺炎、アレルギー疾患

Academic Significance and Societal Importance of the Research Achievements

IPFの根本治療は肺移植しか存在しないことから、IPFは呼吸器診療において最も新規治療薬の開発が待たれている疾患の一つであると言える。本研究から、マクロファージ由来のIGF-1が肺線維芽細胞に直接作用し、サイトカイン産生を誘導することが判明したが、IGF-1は肺以外にも生体維持機構で重要な役割を演じるため、治療標的にしにくい現状がある。本研究から、IGF-1がマクロファージ由来と考えられ、治療標的細胞を肺胞マクロファージに絞った上で治療標的にしうる可能性が示唆された。