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. 1980 Aug;29(2):583–589. doi: 10.1128/iai.29.2.583-589.1980

Inhibition of lymphocyte proliferative responses by ribavirin.

D L Peavy, W C Koff, D S Hyman, V Knight
PMCID: PMC551161  PMID: 7216427

Abstract

When added to cultures of human peripheral blood lymphocytes, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibited antigen- and mitogen-induced proliferative responses as determined by [3H]thymidine incorporation. Dose-dependent suppressive effects were obtained when concentrations of 5 to 60 microgram of ribavirin per ml were added at culture initiation or up to 96 h thereafter. Ribavirin inhibited [3H]uridine and [3H]leucine incorporation by concanavalin A-activated and normal lymphocytes although not as severely as deoxyribonucleic acid synthesis. The capacity of ribavirin to interfere with lymphoproliferative responses was entirely reversed by guanosine and, to a lesser extent, by adenosine and xanthosine. These studies demonstrate that ribavirin is a reversible inhibitor of lymphocyte nucleic acid synthesis and suggest that the drug may be immunosuppressive when administered in vivo.

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Selected References

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

  1. Berendt R. F., Walker J. S., Dominik J. W., Stephen E. L. Response of influenza virus-infected mice to selected doses of ribavirin administered intraperitoneally or by aerosol. Antimicrob Agents Chemother. 1977 Jun;11(6):1069–1070. doi: 10.1128/aac.11.6.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cambridge G., Mackenzie J. S., Keast D. Cell-mediated immune response to influenza virus infections in mice. Infect Immun. 1976 Jan;13(1):36–43. doi: 10.1128/iai.13.1.36-43.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Drach J. C., Shipman C., Jr The selective inhibition of viral DNA synthesis by chemotherapeutic agents: an indicator of clinical usefulness? Ann N Y Acad Sci. 1977 Mar 4;284:396–409. doi: 10.1111/j.1749-6632.1977.tb21976.x. [DOI] [PubMed] [Google Scholar]
  4. Durr F. E., Lindh H. F., Forbes M. Efficacy of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide against influenza virus infections in mice. Antimicrob Agents Chemother. 1975 May;7(5):582–586. doi: 10.1128/aac.7.5.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eriksson B., Helgstrand E., Johansson N. G., Larsson A., Misiorny A., Norén J. O., Philipson L., Stenberg K., Stening G., Stridh S. Inhibition of influenza virus ribonucleic acid polymerase by ribavirin triphosphate. Antimicrob Agents Chemother. 1977 Jun;11(6):946–951. doi: 10.1128/aac.11.6.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goswami B. B., Borek E., Sharma O. K., Fujitaki J., Smith R. A. The broad spectrum antiviral agent ribavirin inhibits capping of mRNA. Biochem Biophys Res Commun. 1979 Aug 13;89(3):830–836. doi: 10.1016/0006-291x(79)91853-9. [DOI] [PubMed] [Google Scholar]
  7. Huffman J. H., Anderson M. A., Allen L. B., Sidwell R. W. Lack of suppression of resistance factors to influenza infections in mice pretreated with virazole. J Antimicrob Chemother. 1977 Jan;3(1):79–85. doi: 10.1093/jac/3.1.79. [DOI] [PubMed] [Google Scholar]
  8. Huffman J. H., Sidwell R. W., Khare G. P., Witkowski J. T., Allen L. B., Robins R. K. In vitro effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses. Antimicrob Agents Chemother. 1973 Feb;3(2):235–241. doi: 10.1128/aac.3.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jolley W. B., Call T. W., Alvord L. S., Hinshaw D. B. Immunosuppressive activity of ribavirin using the rabbit skin allograft model. Ann N Y Acad Sci. 1977 Mar 4;284:230–232. doi: 10.1111/j.1749-6632.1977.tb21954.x. [DOI] [PubMed] [Google Scholar]
  10. Katz E., Margalith E., Winer B. Inhibition of vaccinia virus growth by the nucleoside analogue 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ribavirin). J Gen Virol. 1976 Aug;32(2):327–330. doi: 10.1099/0022-1317-32-2-327. [DOI] [PubMed] [Google Scholar]
  11. Klassen L. W., Budman D. R., Williams G. W., Steinberg A. D., Gerber N. L. Ribavirin: efficacy in the treatment of murine autoimmune disease. Science. 1977 Feb 25;195(4280):787–789. doi: 10.1126/science.299957. [DOI] [PubMed] [Google Scholar]
  12. Klassen L. W., Williams G. W., Reinertsen J. L., Gerber N. L., Steinberg A. D. Ribavirin treatment in murine autoimmune disease. I. Therapeutic efficacy and effect on the immune response. Arthritis Rheum. 1979 Feb;22(2):145–154. doi: 10.1002/art.1780220207. [DOI] [PubMed] [Google Scholar]
  13. Koff W. C., Peavy D. L., Knight V. Inhibition of in vitro proliferative responses of human lymphocytes by rimantadine hydrochloride. Infect Immun. 1979 Mar;23(3):665–669. doi: 10.1128/iai.23.3.665-669.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larson E. W., Stephen E. L., Walker J. S. Therapeutic effects of small-particle aerosols of ribavirin on parainfluenza (sendai) virus infections of mice. Antimicrob Agents Chemother. 1976 Oct;10(4):770–772. doi: 10.1128/aac.10.4.770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Larsson A., Stenberg K., Oberg B. Reversible inhibition of cellular metabolism by ribavirin. Antimicrob Agents Chemother. 1978 Feb;13(2):154–158. doi: 10.1128/aac.13.2.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lowe J. K., Brox L., Henderson J. F. Consequences of inhibition of guanine nucleotide synthesis by mycophenolic acid and virazole. Cancer Res. 1977 Mar;37(3):736–743. [PubMed] [Google Scholar]
  17. Magnussen C. R., Douglas R. G., Jr, Betts R. F., Roth F. K., Meagher M. P. Double-blind evaluation of oral ribavirin (Virazole) in experimental influenza A virus infection in volunteers. Antimicrob Agents Chemother. 1977 Oct;12(4):498–502. doi: 10.1128/aac.12.4.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Martin D. K., Nelms D. C., Mackler B. F., Peavy D. L. Lymphoproliferative responses induced by streptococcal antigens in recurrent aphthous stomatitis and Behcet's syndrome. Clin Immunol Immunopathol. 1979 Jun;13(2):146–155. doi: 10.1016/0090-1229(79)90058-8. [DOI] [PubMed] [Google Scholar]
  19. Müller W. E., Maidhof A., Taschner H., Zahn R. K. Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide; a cytostatic agent. Biochem Pharmacol. 1977 Jun 1;26(11):1071–1075. doi: 10.1016/0006-2952(77)90246-5. [DOI] [PubMed] [Google Scholar]
  20. Potter C. W., Phair J. P., Vodinelich L., Fenton R., Jennings R. Antiviral, immunosuppressive and antitumour effects of ribavirin. Nature. 1976 Feb 12;259(5543):496–497. doi: 10.1038/259496a0. [DOI] [PubMed] [Google Scholar]
  21. Russell A. S. Therapeutic trials with levamisole and other agents in NZB/W mice. J Rheumatol. 1976 Dec;3(4):380–383. [PubMed] [Google Scholar]
  22. Sidwell R. W., Huffman J. H., Khare G. P., Allen L. B., Witkowski J. T., Robins R. K. Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science. 1972 Aug 25;177(4050):705–706. doi: 10.1126/science.177.4050.705. [DOI] [PubMed] [Google Scholar]
  23. Smith C. M., Fontenelle L. J., Muzik H., Paterson A. R., Unger H., Brox L. W., Henderson J. F. Inhibitors of inosinate dehydrogenase activity in Ehrlich ascites tumor cells in vitro. Biochem Pharmacol. 1974 Oct 1;23(19):2727–2735. doi: 10.1016/0006-2952(74)90043-4. [DOI] [PubMed] [Google Scholar]
  24. Stephen E. L., Jahrling P. B. Experimental Lassa fever virus infection successfully treated with ribavirin. Lancet. 1979 Feb 3;1(8110):268–269. doi: 10.1016/s0140-6736(79)90790-6. [DOI] [PubMed] [Google Scholar]
  25. Streeter D. G., Witkowski J. T., Khare G. P., Sidwell R. W., Bauer R. J., Robins R. K., Simon L. N. Mechanism of action of 1- -D-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole), a new broad-spectrum antiviral agent. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1174–1178. doi: 10.1073/pnas.70.4.1174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Witkowski J. T., Robins R. K., Sidwell R. W., Simon L. N. Design, synthesis, and broad spectrum antiviral activity of 1- -D-ribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides. J Med Chem. 1972 Nov;15(11):1150–1154. doi: 10.1021/jm00281a014. [DOI] [PubMed] [Google Scholar]
  27. Wyde P. R., Peavy D. L., Cate T. R. Morphological and cytochemical characterization of cells infiltrating mouse lungs after influenza infection. Infect Immun. 1978 Jul;21(1):140–146. doi: 10.1128/iai.21.1.140-146.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zimmerman T. P., Deeprose R. D. Metabolism of 5-amino-1-beta-D-ribofuranosylimidazole-4-carboxamide and related five-membered heterocycles to 5'-triphosphates in human blood and L5178Y cells. Biochem Pharmacol. 1978 Mar 1;27(5):709–716. doi: 10.1016/0006-2952(78)90508-7. [DOI] [PubMed] [Google Scholar]

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