Pyran and Polyribonucleotides: Differences in Biological Activities

Antimicrob Agents Chemother. 1972 July; 2(1): 16–22.

PMCID: PMC444259

Page S. Morahan, William Regelson, and Albert E. Munson

¹Departments of Medicine and Microbiology, Medical College of Virginia, Health Sciences Division, Virginia Commonwealth University, Richmond, Virginia 23219

This article has been cited by other articles in PMC.

Abstract

Maleic anhydride-divinyl ether copolymer (pyran) and the polyribonucleotides are both large polyanions with potent antiviral activity. However, they are biologically quite different. Interferon levels of 100 units or more/ml were associated with antiviral activity of polyribonucleotides. Interferon induction by pyran compounds was not primarily involved in antiviral resistance because preparations that did not induce interferon possessed antiviral activity equal to that of interferoninducing preparations. Both polyriboinosinic-cytidylic acid [poly (rI.rC)] and pyran increased the immune response to sheep erythrocytes in the Jerne hemolytic plaque-forming cell (PFC) assay, but their modes of immunoadjuvant action differed. On peak day, poly (rI.rC)-treated mice demonstrated 5.1 × 10⁴ PFC/spleen (557 PFC/10⁶ nucleated cells) and pyran-treated mice exhibited 4.5 × 10⁴ PFC/spleen (299 PFC/10⁶ nucleated cells), as compared with 2.7 × 10⁴ PFC/spleen (261 PFC/10⁶ nucleated cells) in controls. The compounds also differed in phagocytic alteration; polyribonucleotides did not affect phagocytosis whereas pyran produced a biphasic response. Both polyanions exhibited toxic inhibition of liver microsomal enzyme metabolism of type I and type II drugs. However, whereas pyran sensitized mice 50-fold to the lethal effects of endotoxin, the polyribonucleotides did not significantly sensitize mice to endotoxin.

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Selected References

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Billiau, A; Muyembe, JJ; De Somer, P. Mechanism of antiviral activity in vivo of polycarboxylases which induce interferon production. Nat New Biol. 1971 Aug 11;232(2):183–186. [PubMed]
Braun, Werner; Nakano, Masayasu. Antibody Formation: Stimulation by Polyadenylic and Polycytidylic Acids. Science. 1967 Aug 18;157(3790):819–821. [PubMed]
Braun, W; Regelson, W; Yajima, Y; Ishizuka, M. Stimulation of antibody formation by pyran copolymer. Proc Soc Exp Biol Med. 1970 Jan;133(1):171–175. [PubMed]
Field, AK; Tytell, AA; Lampson, GP; Hilleman, MR. Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes. Proc Natl Acad Sci U S A. 1967 Sep;58(3):1004–1010. [PubMed]
Gram, TE; Wilson, JT; Fouts, JR. Some characteristics of hepatic microsomal systems which metabolize aminopyrine in the rat and rabbit. J Pharmacol Exp Ther. 1968 Jan;159(1):172–181. [PubMed]
Huang, KY; Landay, ME. Enhancement of the lethal effects of endotoxins by interferon inducers. J Bacteriol. 1969 Nov;100(2):1110–1111. [PubMed]
Jerne, Niels K; Nordin, Albert A. Plaque Formation in Agar by Single Antibody-Producing Cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed]
Levy, HB; Law, LW; Rabson, AS. Inhibition of tumor growth by polyinosinic-polycytidylic acid. Proc Natl Acad Sci U S A. 1969 Feb;62(2):357–361. [PubMed]
Merigan, TC. Induction of circulating interferon by synthetic anionic polymers of known composition. Nature. 1967 Apr 22;214(5086):416–417. [PubMed]
Merigan, TC; Finkelstein, MS. Interferon-stimulating and in vivo antiviral effects of various synthetic anionic polymers. Virology. 1968 Jul;35(3):363–374. [PubMed]
Merigan, TC; Regelson, W. Interferon induction in man by a synthetic polyanion of defined composition. N Engl J Med. 1967 Dec 14;277(24):1283–1287. [PubMed]
MORROW, SH; DILUZIO, NR. THE FATE OF FOREIGN RED CELLS IN MICE WITH ALTERED RETICULOENDOTHELIAL FUNCTION. Proc Soc Exp Biol Med. 1965 Jul;119:647–652. [PubMed]
Munson, AE; Regelson, W; Lawrence, W, Jr; Wooles, WR. Biphasic response of the reticuloendothelial system (RES) induced by pyran copolymer. J Reticuloendothel Soc. 1970 Mar;7(3):375–385. [PubMed]
Pindak, FF; Schmidt, JP; Giron, DJ; Allen, PT. Interferon levels and resistance to viral infection associated with selected interferon inducers. Proc Soc Exp Biol Med. 1971 Oct;138(1):317–321. [PubMed]
Richmond, JY; Hamilton, LD. Foot-and-mouth disease virus inhibition induced in mice by synthetic double-stranded RNA (polyriboinosinic and polyribocytidylic acids). Proc Natl Acad Sci U S A. 1969 Sep;64(1):81–86. [PubMed]
Sandberg, J; Goldin, A. Use of first generation transplants of a slow growing solid tumor for the evaluation of new cancer chemotherapeutic agents. Cancer Chemother Rep. 1971 Jun;55(3):233–238. [PubMed]
Turner, W; Chan, SP; Chirigos, MA. Stimulation of humoral and cellular antibody formation in mice by poly Ir:Cr. Proc Soc Exp Biol Med. 1970 Jan;133(1):334–338. [PubMed]