TABLE 2.
Qualitative summary of the in vivo efficacy of nintedanib in animal models of lung fibrosis
| Bleomycin-induced lung fibrosis | Silica-induced lung fibrosis | |||||
| Rat | Mouse | Mouse | ||||
| Model | Preventive | Therapeutic | Preventive | Therapeutic | Preventive | Therapeutic# |
| Histology | ||||||
| Fibrosis | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ |
| Inflammation | ND | ND | ↓ | ↓ | ↓ | ↓ |
| Granuloma | ND | ND | ND | ND | ↓ | ↓ |
| Lung tissue | ||||||
| TGF-β mRNA | ↓ | ↓ | ND | ND | ND | ND |
| Procollagen-1 mRNA | ↓ | ↓ | ND | ND | ND | ND |
| Total collagen | ND | ND | – | ↓ | ↓ | ↓ |
| IL-1β | ND | ND | ↓ | ↓ | ↓ | ↓ |
| IL-6 | ND | ND | ND | ND | ND | ↓ |
| CXCL1/KC | ND | ND | – | – | ↓ | ↓ |
| TIMP-1 | ND | ND | ↓ | ↓ | ↓ | ↓ |
| BALF | ||||||
| Total cells | ND | ND | – | – | – | – |
| Macrophages | ND | ND | – | – | – | – |
| Neutrophils | ND | ND | ND | ND | ↓ | ↓ |
| Lymphocytes | ND | ND | ↓ | ↓ | ↓ | ↓ |
↓: significant reduction (independent of dose used); –: no significant effect (independent of dose used); ND: not determined; TGF: transforming growth factor; IL: interleukin; TIMP: tissue inhibitors of metalloproteinase; BALF: bronchoalveolar lavage fluid. #: therapeutic treatment starting on day 10. Data from [78].