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. 1977 Jun;11(6):984–992. doi: 10.1128/aac.11.6.984

Comparation Interferon-Inducing and Antiviral Properties of 2-Amino-5-Bromo-6-Methyl-4-Pyrimidinol (U-25,166), Tilorone Hydrochloride, and Polyinosinic-Polycytidylic Acid

Dale A Stringfellow 1
PMCID: PMC352115  PMID: 879763

Abstract

2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), polyinosinic acid-polycytidylic acid [poly(I:C)], and tilorone HCl induced high levels of serum interferon in mice. Each consequently protected mice against infection with several viruses. After daily injection of inducer, mice developed a reduced interferon response (hyporeactivity) to each compound. However, hyporeactivity developed more slowly to U-25,166 and poly(I:C) than to tilorone HCl. After onset of hyporeactivity, 5 to 6 days without each inducer were required before normal serum interferon levels could be stimulated. Animals also developed a hyporeactive state as a consequence of Semliki Forest or encephalomyocarditis virus infections. By day 2 of either infection, mice had a suppressed interferon response to tilorone HCl, but remains responsive to poly(I:C) or U-25,166 until day 4. In vivo, poly(I:C) stimulated interferon production in a variety of cells and organs, whereas the tilorone HCl and U-25,166 responses involved a nonlymphoid component of the reticuloendothelial system. In vitro, poly(I:C) induced interferon in a variety of murine cells, U-25,166 was active in murine thymus and spleen organ cultures, and tilorone was inactive. These data indicate that U-25,166 is an interesting low-molecular-weight interferon inducer.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. De Clercq E., Merigan T. C. Bis-DEAE-fluorenone: mechanism of antiviral protection and stimulation of interferon production in the mouse. J Infect Dis. 1971 Feb;123(2):190–199. doi: 10.1093/infdis/123.2.190. [DOI] [PubMed] [Google Scholar]
  2. De Maeyer E., De Maeyer-Guignard J., Jullien P. Inter- feron synthesis in x-irradiated animals. 3. The high radiosensitivity of myxovirus-induced circulating interferon production. Proc Soc Exp Biol Med. 1969 May;131(1):36–41. doi: 10.3181/00379727-131-33799. [DOI] [PubMed] [Google Scholar]
  3. Field A. K., Tytell A. A., Lampson G. P., Hilleman M. R. Inducers of interferon and host resistance, V. In vitro studies. Proc Natl Acad Sci U S A. 1968 Sep;61(1):340–346. doi: 10.1073/pnas.61.1.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Glasgow L. A. Immunosuppression, interferon, and viral infections. Fed Proc. 1971 Nov-Dec;30(6):1846–1851. [PubMed] [Google Scholar]
  5. Greenberg H. B., Pollard R. B., Lutwick L. I., Gregory P. B., Robinson W. S., Merigan T. C. Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med. 1976 Sep 2;295(10):517–522. doi: 10.1056/NEJM197609022951001. [DOI] [PubMed] [Google Scholar]
  6. Hilleman M. R. Toward control of viral infections of man. Science. 1969 May 2;164(3879):506–514. doi: 10.1126/science.164.3879.506. [DOI] [PubMed] [Google Scholar]
  7. Hoffman W. W., Korst J. J., Niblack J. F., Cronin T. H. N,N-dioctadecyl-N',N'-bis(2-hydroxyethyl) propanediamine: antiviral activity and interferon stimulation in mice. Antimicrob Agents Chemother. 1973 Apr;3(4):498–502. doi: 10.1128/aac.3.4.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jullien P., De Maeyer-Guignard J., De Maeyer E. Interferon synthesis in x-irradiated animals v. Origin of mouse serum interferon induced by polyinosinic-polycytidylic Acid and encephalomyocarditis virus. Infect Immun. 1974 Nov;10(5):1023–1028. doi: 10.1128/iai.10.5.1023-1028.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krueger R. E., Mayer G. D. Tilorone hydrochloride: an orally active antiviral agent. Science. 1970 Sep 18;169(3951):1213–1214. doi: 10.1126/science.169.3951.1213. [DOI] [PubMed] [Google Scholar]
  10. Mayer G. D., Krueger R. F. Tilorone hydrochloride: mode of action. Science. 1970 Sep 18;169(3951):1214–1215. doi: 10.1126/science.169.3951.1214. [DOI] [PubMed] [Google Scholar]
  11. Merigan T. C., Reed S. E., Hall T. S., Tyrrell D. A. Inhibition of respiratory virus infection by locally applied interferon. Lancet. 1973 Mar 17;1(7803):563–567. doi: 10.1016/s0140-6736(73)90714-9. [DOI] [PubMed] [Google Scholar]
  12. Nichol F. R., Weed S. D., Underwood G. E. Stimulation of murine interferon by a substituted pyrimidine. Antimicrob Agents Chemother. 1976 Mar;9(3):433–439. doi: 10.1128/aac.9.3.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Panusarn C., Stanley E. D., Dirda V., Rubenis M., Jackson G. G. Prevention of illness from rhinovirus infection by a topical interferon inducer. N Engl J Med. 1974 Jun 11;291(2):57–61. doi: 10.1056/NEJM197407112910201. [DOI] [PubMed] [Google Scholar]
  14. Stringfellow D. A., Glasgow L. A. Hyporeactivity of infection: potential limitation to therapeutic use of interferon-inducing agents. Infect Immun. 1972 Nov;6(5):743–747. doi: 10.1128/iai.6.5.743-747.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stringfellow D. A., Glasgow L. A. Tilorone hydrochloride: an oral interferon-inducing agent. Antimicrob Agents Chemother. 1972 Aug;2(2):73–78. doi: 10.1128/aac.2.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Stringfellow D. A., Kern E. R., Kelsey D. K., Glasgow L. A. Suppressed response to interferon inducation in mice infected with encephalomyocarditis virus, Semliki forest virus, influenza A2 virus, Herpesvirus hominis type 2, or murine cytomegalovirus. J Infect Dis. 1977 Apr;135(4):540–551. doi: 10.1093/infdis/135.4.540. [DOI] [PubMed] [Google Scholar]
  17. de Maeyer-Guignard J., de Maeyer E. Effect of antilymphocytic serum on circulating interferon in mice as a function of the inducer. Nat New Biol. 1971 Feb 17;229(7):212–214. doi: 10.1038/newbio229212a0. [DOI] [PubMed] [Google Scholar]

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