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Pulmonary fibrosis (interstitial lung fibrosis) has a varied etiology; including inflammatory diseases and injury, aging, environmental exposures (e.g. asbestos, silica, radiation, etc.); drug administration (e.g. bleomycin, amidarone, isothiocyanate, etc.), and idiopathic origins.
For researchers, pre-clinical pulmonary fibrosis model selection requires an assessment of the most appropriate model for the recapitulation of the fibrosis form under study, balanced with considerations around the advantages and disadvantages of each particular model.
Read more about the most common small animal fibrosis models, along with a brief description of their modes of induction, advantages, and disadvantages.
Bleomycin-induced fibrosis is by far the best characterised and most widely used pre-clinical pulmonary fibrosis model. Indeed, bleomycin has been recommended in the ATS (American Thoracic Society) workshop report for initial pre-clinical therapy assessments5. Bleomycin is an antineoplastic glycopeptide, originating from Streptomyces verticillus, and toxicity occurs in tissues with relative under expression of the bleomycin hydrolase, such as the lung6.
Several guides to bleomycin model development are available, providing in depth discussion on experimental design, considerations and expected pathological outcomes.
Endotracheal bleomycin delivery (often performed, with the now unavailable, Penn Century Microsprayer), intravenous or intraperitoneal administration are possible, whether that be via single or repeated administrations. Systemic delivery causes more diffuse fibrosis with a longer time course, and endotracheal delivery is the more common approach. More recently, ventilator-assisted drug delivery is emerging as a potential methodology for bleomycin delivery, possibly limiting some of the heterogeneity of endotracheal instillation7.
