BACKGROUND: Nintedanib, a tyrosine kinase inhibitor that is specific for 
platelet-derived growth factor receptors (PDGFR), fibroblast growth factor 
receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has 
recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone 
marrow-derived progenitor cells that produce growth factors and contribute to 
fibrogenesis in the lungs. However, the effects of nintedanib on the functions 
of fibrocytes remain unclear.
METHODS: Human monocytes were isolated from the peripheral blood of healthy 
volunteers. The expression of growth factors and their receptors in fibrocytes 
was analyzed using ELISA and Western blotting. The effects of nintedanib on the 
ability of fibrocytes to stimulate lung fibroblasts were examined in terms of 
their proliferation. The direct effects of nintedanib on the differentiation and 
migration of fibrocytes were also assessed. We investigated whether nintedanib 
affected the accumulation of fibrocytes in mouse lungs treated with bleomycin.
RESULTS: Human fibrocytes produced PDGF, FGF2, and VEGF-A. Nintedanib and 
specific inhibitors for each growth factor receptor significantly inhibited the 
proliferation of lung fibroblasts stimulated by the supernatant of fibrocytes. 
Nintedanib inhibited the migration and differentiation of fibrocytes induced by 
growth factors in vitro. The number of fibrocytes in the bleomycin-induced lung 
fibrosis model was reduced by the administration of nintedanib, and this was 
associated with anti-fibrotic effects.
CONCLUSIONS: These results support the role of fibrocytes as producers of and 
responders to growth factors, and suggest that the anti-fibrotic effects of 
nintedanib are at least partly mediated by suppression of fibrocyte function.