Pulmonary Fibrosis

 

 

Clinical Background

Idiopathic pulmonary fibrosis is a lethal lung disease characterized by the progressive formation of fibroblasts, accumulation of extracellular matrix and decrease in pulmonary function. Current treatments include corticosteroids and other immunosuppressants, but they have limited success. It is believed that antifibrotic agents may have the capability to impede the progression toward chronic pulmonary failure.
 
 

Preclinical Models

Model Description Length Endpoints
Intratracheal bleomycin-induced pulmonary fibrosis
Bleomycin introduced directly to lungs via cannula 21 days Weight and respiratory status; weight, collagen content, and fibrosis score of lungs
Intravenous bleomycin-induced pulmonary fibrosis
Bleomycin introduced intravenously for 5 days 42 days Weight and respiratory status; weight, collagen content, and fibrosis score of lungs

 
 

Intratracheal Bleomycin-Induced Pulmonary Fibrosis

The bleomycin-induced pulmonary fibrosis model is the standard model of human lung fibrosis. After being anesthetized, animals have a cannula inserted into the trachea and down into the lungs and then bleomycin is slowly infused into the lungs. Animals are evaluated daily for body weight and respiratory status. After animals are sacrificed, lung weight, collagen content and fibrosis scores are determined.
 
 

Mean Modified Ashcroft Fibrosis Score Intratracheal(IT) Bleomycin

*Fibrosis scores resulting from intratracheal bleomycin exposure

 
 

Lung Collagen Content (hyrdroxyprouine – based) intratracheal(IT) Bleomycin

*Lung collagen content resulting from intratracheal bleomycin exposure

 
 

Mean Wet Lung Weight intratracheal(IT) Bleomycin

*Wet lung weight resulting from intratracheal bleomycin exposure

 
 

Bleomycin-induced fibrosis: Ashcroft score = 6
(4x Magnification) Majority of space is effaced by fibrosis (bound by arrows) with secondary nodules of fibrosis (dashed arrows)

Bleomycin-induced fibrosis: Ashcroft score = 6
(40x Magnification) Virtually entire field replaced by fibrosis with only a few scattered alveoli remaining visible (asterisk).

 
 

Intravenous Bleomycin-Induced Pulmonary Fibrosis

The bleomycin-induced pulmonary fibrosis model is the standard model of human lung fibrosis. Animals are are given intravenous (i.v.) dosing with bleomycin for days 0-4 and are evaluated daily for body weight and respiratory status. After animals are sacrificed, lung weight, collagen content and fibrosis scores are determined.
 
 

Mean Modified Ashcroft Fibrosis Score Intravenous (i.v.) Bleomycin (q.d. Days 0-4)

*Fibrosis scores resulting from intravenous bleomycin exposure

 
 

Mean Lung Collagen Content Intravenous (i.v.) Bleomycin (q.d. Days 0-4)

*Lung collagen content resulting from intravenous bleomycin exposure

 
 

Mean Wet Lung Weight Intravenous (i.v.) Bleomycin (q.d. Days 0-4)

*Wet lung weight resulting from intratracheal bleomycin exposure

 
 

Bleomycin-induced fibrosis: Ashcroft score = 5
(4x Magnification) Arrows show areas of subpleural fibrosis that extend into pulmonary parenchyma and effacing ~30% of section

Bleomycin-induced fibrosis: Ashcroft score = 5
(40x Magnification) Alveolar walls thickened by fibrosis (most visible at arrows) admixed with scattered inflammatory cells

 
 

Publications

Bleomycin revisited: towards a more representative model of IPF?
Chris J. Scotton and Rachel C. Chambers
Am J Physiol Lung Cell Mol Physiol DOI: 10.1152/ajplung.00258.2010

 

 

Mechanisms of cellular fibrosis associated with cancer regimen-related toxicities.
Mancini ML, Sonis ST. Front. Pharmacol. 5:51. doi: 10.3389