Antiviral activity and side effects of polyriboinosinic-cytidylic acid complexes as affected by molecular size.
The decrease of the molecular size of poly(I.C) to less than 10(6) decreases its ability to induce interferon, protect mice against virus, or enhance the immune response. Immune adjuvant activity appeared more sensitive to molecular weight than the other protective activities. The composition of the complex-the molecular size of the individual homopolymers when one was large and the other small-did not affect antiviral activity; the activity of a complex made from large poly(I) and small poly(C) was similar to one made from small poly(I) and large poly(C). Molecular size of the complex did not profoundly alter the side effects of poly(I.C). At 2 mg/kg, none of the complexes markedly altered phagocytic function. Only the largest complex sensitized the mouse to endotoxin. However, all of the complexes studied profoundly inhibited drug metabolism by the liver microsomal enzymes between 24 and 72 hr after their inoculation. Decreasing the molecular weight did not alter this inhibition.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002499:Centrifugation, Density Gradient; D002859:Chromium Isotopes; D004686:Encephalomyocarditis virus / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D006386:Hemagglutination Tests; D006591:Hexobarbital / Q000378:metabolism; D007372:Interferons / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D010088:Oxidoreductases / Q000378:metabolism; D010587:Phagocytosis; D011070:Poly I-C / Q000494:pharmacology / Q000627:therapeutic use; D011119:Polynucleotides / Q000494:pharmacology*; D012756:Sheep; D013329:Structure-Activity Relationship; D014777:Virus Diseases / Q000188:drug therapy
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002859:Chromium Isotopes; D004731:Endotoxins; D011119:Polynucleotides; D000632:Aminopyrine; D007372:Interferons; D006591:Hexobarbital; D010088:Oxidoreductases; D011070:Poly I-C