Dose and regimen effects of poly ICLC, an interferon inducer, in a multi-dose bleomycin model of interstitial pulmonary fibrosis

J. S. Wild, D. M. Hyde, S. N. Giri

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Abstract

The antifibrotic effects of an interferon inducer, Polyinosinic-polycytidylic acid complexed with poly-L-lysine (poly ICLC), was evaluated in a bleomycin-hamster model of pulmonary fibrosis. Hamsters received three consecutive intratracheal doses of bleomycin (2.5, 2.0, and 1.5 U/kg/5 ml) or saline at weekly intervals. Poly ICLC at three doses (0.5, 1.0, and 1.5 mg/kg body weight) or saline was injected intraperitoneally by daily and semiweekly regimens for four weeks, and animals were sacrificed at five weeks. In both the daily and semiweekly poly ICLC regimens, hamsters receiving bleomycin plus poly ICLC demonstrated increased mortality and decreased weight gain compared to the vehicle and bleomycin control groups. The groups receiving bleomycin plus daily poly ICLC demonstrated poly ICLC-dose related effects for weight changes, lung hydroxyproline and lung prolyl hydroxylase activity. Depending on the poly ICLC dose, bleomycin plus daily poly ICLC produced significantly decreased hydroxyproline or signifcantly increased hydroxyproline and prolyl hydroxylase activity compared to the bleomycin control group. In contrast, the groups receiving bleomycin plus semiweekly poly ICLC did not demonstrate poly ICLC-dose related effects or significant differences from the bleomycin control group for any of the biochemical assays performed. The results of this study indicate that, depending on dose and regimen, poly ICLC can reduce collagen accumulation or produce a synergistic toxicity when administered with multiple doses of bleomycin. The toxic effects may restrict the therapeutic potential of poly ICLC in combination with bleomycin for anticancer therapy.

Original languageEnglish (US)
Pages (from-to)42-48
Number of pages7
JournalPharmacology and Toxicology
Volume75
Issue number1
StatePublished - 1994

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Interferon Inducers
Pulmonary Fibrosis
Bleomycin
Hydroxyproline
Cricetinae
Prolyl Hydroxylases
Control Groups
poly ICLC
Poly I-C
Lung
Poisons
Lysine
Weight Gain
Toxicity

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Toxicology

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Dose and regimen effects of poly ICLC, an interferon inducer, in a multi-dose bleomycin model of interstitial pulmonary fibrosis. / Wild, J. S.; Hyde, D. M.; Giri, S. N.

In: Pharmacology and Toxicology, Vol. 75, No. 1, 1994, p. 42-48.

Research output: Contribution to journalArticle

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abstract = "The antifibrotic effects of an interferon inducer, Polyinosinic-polycytidylic acid complexed with poly-L-lysine (poly ICLC), was evaluated in a bleomycin-hamster model of pulmonary fibrosis. Hamsters received three consecutive intratracheal doses of bleomycin (2.5, 2.0, and 1.5 U/kg/5 ml) or saline at weekly intervals. Poly ICLC at three doses (0.5, 1.0, and 1.5 mg/kg body weight) or saline was injected intraperitoneally by daily and semiweekly regimens for four weeks, and animals were sacrificed at five weeks. In both the daily and semiweekly poly ICLC regimens, hamsters receiving bleomycin plus poly ICLC demonstrated increased mortality and decreased weight gain compared to the vehicle and bleomycin control groups. The groups receiving bleomycin plus daily poly ICLC demonstrated poly ICLC-dose related effects for weight changes, lung hydroxyproline and lung prolyl hydroxylase activity. Depending on the poly ICLC dose, bleomycin plus daily poly ICLC produced significantly decreased hydroxyproline or signifcantly increased hydroxyproline and prolyl hydroxylase activity compared to the bleomycin control group. In contrast, the groups receiving bleomycin plus semiweekly poly ICLC did not demonstrate poly ICLC-dose related effects or significant differences from the bleomycin control group for any of the biochemical assays performed. The results of this study indicate that, depending on dose and regimen, poly ICLC can reduce collagen accumulation or produce a synergistic toxicity when administered with multiple doses of bleomycin. The toxic effects may restrict the therapeutic potential of poly ICLC in combination with bleomycin for anticancer therapy.",
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