A Highly Reproducible In Vivo Model For Bleomycin-Induced Lung Fibrosis In Mice To Evaluate Drugs For The Treatment Of IPF

Overview
Idiopathic pulmonary fibrosis (IPF) is a type of chronic lung disease characterized by a progressive and irreversible decline in lung function. It is a progressive and ultimately fatal disease that causes scarring and thickening of the lung tissue, leading to respiratory failure.

The cause of IPF remains unknown; however, some risk factors include cigarette smoking, gastroesophageal reflux, specific environmental exposures, viral infection, and age. A genetic predisposition may also be a factor. (Drugs R D. 2018 Mar; 18(1): 19–25).

IPF is believed to be the result of an aberrant wound healing process involving abnormal and excessive deposition of collagen (fibrosis) in the pulmonary interstitium with minimal associated inflammation.

Treatments
In recent years, both Pirfenidone and Nintedanib have been approved for use in multiple countries for treatment of IPF. Pirfenidone (5-methyl-1-phenyl-2-[1H]- pyridone) is an orally administered drug with antifibrotic, anti-inflammatory, and antioxidant effects as shown in preclinical studies (Core Evid. 2016; Jul 1; 11: 11–22). Nintedanib is a tyrosine kinase inhibitor. Both drugs have been shown to slow idiopathic pulmonary fibrosis progression and have an acceptable tolerability profile.

Despite the moderate success of Pirfenidone and Nintedanib, additional treatment options are needed and lung fibrosis remains a major unmet medical need.

Pre-clinical Research
Bleomycin-induced pulmonary fibrosis has been a useful preclinical model in several species and is most prevalent in rodent models to evaluate potential prophylactic and therapeutic drugs for IPF. As a tissue injury and repair model of fibrosis, bleomycin (BLM) has contributed significantly to studies of the pathobiology of pulmonary fibrosis. The induction and progression of the disease in rodents is of a short duration, making it a practical model for evaluating test compounds in preclinical research. Major drawbacks for this model have been its mortality rate and inconsistency in the induction of the disease.