Ameliorating effect of an interferon inducer polyinosinic-polycytidylic acid on bleomycin-induced lung fibrosis in hamsters. Morphologic and biochemical evidence.
The effects of polyinosinic-polycytidylic acid (Poly I:C), an inducer of interferons, on bleomycin (Bleo)-induced lung fibrosis was studied in hamsters. Poly I:C (10 mg/kg intraperitoneally) was administered for two days and immediately before intratracheal instillation of bleomycin (7.5 U/kg) or an equivalent volume of saline and thereafter daily for 13 days. The lung hydroxyproline in control, Poly I:C, Bleo, and Bleo + Poly I:C groups averaged 791, 752, 1177, and 766 micrograms/lung. As compared to control, the prolyl hydroxylase activity in the Bleo group was increased by 83% whereas in Bleo + Poly I:C group, the activity was increased by 42%. Protein in the bronchoalveolar lavage supernatant in Poly I:C, Bleo and Bleo + Poly I:C groups were 72, 286, and 206% of the control, respectively. There was no difference in total leukocyte counts between Bleo + Poly I:C and Bleo groups, but the differential cell counts were changed. The numbers of neutrophils, monocytes, lymphocytes, and eosinophils were 50, 84, 91, and 10% of Bleo group, respectively. Morphometric estimates of the volume of parenchymal lesion within the lung showed that hamsters in Bleo + Poly I:C group had significantly less volume of lesion (1.0 cucm) than the Bleo group (1.6 cucm). In addition, the fibrotic lesions in Bleo + Poly I:C group were multifocal and primarily proximal acinar in location, had fewer extracellular fibers, neutrophils and monocytes. Poly I:C treatment ameliorated bleomycin-induced lung collagen accumulation.
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Department of Veterinary Pharmacology and Toxicology, School of Veterinary Medicine, University of California, Davis 95616.
Hyde
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D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000166:cytology; D003094:Collagen / Q000032:analysis; D006224:Cricetinae; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000032:analysis / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008647:Mesocricetus; D008854:Microscopy, Electron; D011070:Poly I-C / Q000627:therapeutic use*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D011506:Proteins; D001761:Bleomycin; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D011070:Poly I-C; D006909:Hydroxyproline