Early CYNC-1 Administration Attenuates Radiation-Induced Lung Inflammation and Subsequent Fibrotic Remodeling

Background/Objectives: Radiation-induced lung injury (RILI) involves inflammatory responses followed by fibrotic remodeling. We evaluated CYNC-1, a synthetic compound designed as a lipoxin A4 (LXA4) mimetic, for chemical stability, cellular activity, and attenuation of lung injury after irradiation.

Methods

HeLa-derived L132 epithelial-like cells and THP1-Lucia NF-κB reporter monocytes were used for cell-based assays. Male C57BL/6 mice received a single 75-Gy focal lung irradiation. CYNC-1 administration began immediately after irradiation and continued every other day for 2 or 6 weeks. Lung injury was assessed using bronchoalveolar lavage fluid cellularity, micro-computed tomography, histopathology, and lung mechanics. Prednisolone and nintedanib served as reference treatments in the 2- and 6-week cohorts, respectively.