The antifibrotic effect of the
mismatched double-stranded RNA,
Ampligen (
poly(I).poly(C12U)), was evaluated in a
bleomycin-mouse model of
pulmonary fibrosis. Mice received a single intratracheal dose of
bleomycin (0.125 U/mouse) or saline (50 microL) at the beginning of the experiment, followed by 5 or 6
intraperitoneal injections of
Ampligen (1.0, 5.0, 10.0, 15.0, or 25.0 mg/kg) or saline at regular intervals for 2 weeks.
Ampligen did not produce increased mortality or
weight loss by itself. However, it produced varying degrees of mortality in combination with
bleomycin. Five
injections of 10 mg/kg
Ampligen or three
injections of 25 mg/kg
Ampligen plus three
injections of 10 mg/kg
Ampligen in combination with
bleomycin .produced significant reductions in lung
collagen accumulation as indicated by lung
hydroxyproline content compared to the
bleomycin control group. Animals receiving
bleomycin plus
Ampligen at all dosages had significantly reduced
prolyl hydroxylase activity compared to the
bleomycin control group. Lipid peroxidation and bronchoalveolar lavage fluid (BALF)-supernatant
protein content for the groups receiving
bleomycin plus
Ampligen were not reduced compared to the
bleomycin control group. In the BALF-supernatant, the activity of
acid phosphatase, a lysosomal
enzyme produced by neutrophils, monocytes, and macrophages, was significantly decreased in the group receiving
bleomycin plus 10 mg/kg
Ampligen. Also, selected BALF differential immune cell counts were reduced in some of the groups receiving
bleomycin plus
Ampligen, but not in a consistent or dose-dependent manner. The results of this study indicate that
Ampligen can significantly reduce the
bleomycin-induced increased
collagen accumulation and may be therapeutically useful in the management of lung
fibrosis in humans.