Dose-related effects of ampligen (poly(I)·poly(C12U)), a mismatched double-stranded RNA, in a bleomycin-mouse model of pulmonary fibrosis

James S. Wild, Dallas M. Hyde, Howard R. Hubbell, Shri N. Giri

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 (0.125U/mouse) or saline (50 μL) 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.

Original languageEnglish (US)
Pages (from-to)375-391
Number of pages17
JournalExperimental Lung Research
Volume22
Issue number3
StatePublished - 1996

Fingerprint

Pulmonary Fibrosis
Bleomycin
Bronchoalveolar Lavage Fluid
poly(I).poly(c12,U)
indium-bleomycin
Lung
Control Groups
Injections
Fluids
Collagen
Prolyl Hydroxylases
Mortality
Macrophages
Hydroxyproline
Acid Phosphatase
Intraperitoneal Injections
Lipid Peroxidation
Weight Loss
Monocytes
Animals

Keywords

  • Ampligen
  • Bleomycin
  • Interferon inducers
  • Mismatched double-stranded RNA
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Dose-related effects of ampligen (poly(I)·poly(C12U)), a mismatched double-stranded RNA, in a bleomycin-mouse model of pulmonary fibrosis. / Wild, James S.; Hyde, Dallas M.; Hubbell, Howard R.; Giri, Shri N.

In: Experimental Lung Research, Vol. 22, No. 3, 1996, p. 375-391.

Research output: Contribution to journalArticle

Wild, James S. ; Hyde, Dallas M. ; Hubbell, Howard R. ; Giri, Shri N. / Dose-related effects of ampligen (poly(I)·poly(C12U)), a mismatched double-stranded RNA, in a bleomycin-mouse model of pulmonary fibrosis. In: Experimental Lung Research. 1996 ; Vol. 22, No. 3. pp. 375-391.
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