Objective: To investigate the effect of murine interferon-gamma (IFN-gamma) transgene expression on bleomycin-induced pulmonary fibrosis in mice.
Methods: 6 - 8 week aged pathogen-free male ICR mice were treated with bleomycin (3 mg/kg weight in 70 micro l) by intranasal instillation on day 0 in the model group. Adenoviral vector with murine IFN-gamma cDNA (AdCMVmIFN-gamma) 5 x 10(8) plague forming unit (pfu) was administrated via nastril instillation 48 h before bleomycin treatment in the preventive therapeutic group, but 72 h after bleomycin treatment in the therapeutic group. Mice treated with a same volume of normal saline (NS) and a same dosage of sham recombinant adenoviruses (AdCMVNull) served as controls. The animals were weighted on day 0, 7, 14, and sacrificed on day 14. Bronchial alveolar lavage fluid (BALF) and lungs were recovered. The right lung was stained with either hematoxylin-eosin or masson. The left lung was weighted, and its content of hydroxyproline (HYP) was measured by HCl acid hydrosis method. The IFN-gamma concentration in BALF was determined with enzyme-linked immunosorbent assay.
Results: The concentrations of IFN-gamma in BALF from the AdCMVmIFN-gamma treated groups were remarkably increased, (21,250 +/- 6,497) pg/ml and (21,000 +/- 5,451) pg/ml in the IFN-gamma transgenetic preventive therapeutic group and the therapeutic group respectively. IFN-gamma was undetectable in BALF from other groups. Mice in the two groups treated with AdCMVmIFN-gamma had statistically significant weight loss (P < 0.05), higher HYP content (P < 0.05), and tended to have more severe alveolitis and pulmonary fibrosis (P = 0.07) as compared with those in other groups.
Conclusions: (1) mIFN-gamma could be overexpressed in airway and alveolar epithelium by locally administrated AdCMVmIFN-gamma. (2) Early mIFN-gamma transgene expression via adenoviral vector in this bleomycin model aggravated alveolitis and fibrosis to some degree.