Related Experiment Video
Updated: Sep 28, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice
1North West Lung Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester, UK.
Abstract:
Studies of human tissue have suggested an association between productive Epstein Barr virus and idiopathic pulmonary fibrosis (IPF). However, a pathogenic role for the virus has not been established. This study was undertaken to develop an animal model, which would explore the association between viral infection and pulmonary fibrosis. BALB/c mice (n=30), resistant to bleomycin, were primed with murine gammaherpesvirus 68 and then given intraperitoneal bleomycin. The mice were sacrificed at 28 days after bleomycin and their lungs assessed histologically and biochemically. Lung pathology was scored 0-3 for fibrotic and inflammatory change. BALB/c mice given virus and bleomycin showed more lung fibrosis (median score 2.2) compared to those given bleomycin alone (median 0), virus alone (median 0.2) or phosphate-buffered saline (PBS) control (median 0). Similarly mice given both virus and bleomycin showed more lung inflammation (median score 1.9) compared to those given bleomycin (median 0.5), virus (median 0.8), or PBS control (median 0.2). There was a significant difference in collagen content between the bleomycin and virus group (mean 1.86 mg) compared to the belomycin alone group (mean 1.52 mg). These results suggest that virus alone does not result in pulmonary fibrosis but that replicating virus in the presence of an exogenous injury may promote the development of pulmonary fibrosis.
Insights
Productive Epstein Barr virus (EBV) may contribute to idiopathic pulmonary fibrosis (IPF). This study developed an animal model showing that replicating EBV with exogenous injury promotes pulmonary fibrosis development.
Area of Science:
- Pulmonary Medicine
- Virology
- Immunology
Background:
- Human tissue studies suggest a link between Epstein Barr virus (EBV) and idiopathic pulmonary fibrosis (IPF).
- A definitive pathogenic role for EBV in IPF has not been established.
- An animal model is needed to investigate the association between viral infection and pulmonary fibrosis.
Purpose of the Study:
- To develop and validate an animal model for studying the role of viral infection in pulmonary fibrosis.
- To investigate the potential pathogenic role of EBV in the development of pulmonary fibrosis.
Main Methods:
- BALB/c mice were primed with murine gammaherpesvirus 68 (a surrogate for EBV) and then administered bleomycin, an inducer of pulmonary fibrosis.
- Lung tissues were assessed histologically and biochemically 28 days post-bleomycin administration.
- Pathology was scored for fibrotic and inflammatory changes, and collagen content was measured.
Main Results:
- Mice receiving both virus and bleomycin exhibited significantly higher scores for lung fibrosis (median 2.2) and inflammation (median 1.9) compared to control groups.
- Bleomycin alone resulted in minimal fibrosis (median 0) and inflammation (median 0.5).
- Collagen content was significantly higher in the virus and bleomycin group (mean 1.86 mg) compared to the bleomycin alone group (mean 1.52 mg).
Conclusions:
- Murine gammaherpesvirus 68 alone does not cause pulmonary fibrosis.
- Replicating virus in conjunction with an exogenous injury, such as bleomycin, promotes the development of pulmonary fibrosis.
- This animal model provides a platform for further research into the viral contribution to IPF pathogenesis.
