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Open Access 01-08-2019 | Herpes Virus | Review

Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases

Authors: Jiri Sliva, Chrysoula N. Pantzartzi, Martin Votava

Published in: Advances in Therapy | Issue 8/2019

Abstract

Inosine pranobex (IP), commonly known as inosine acedoben dimepranol, isoprinosine and methisoprinol, has been proven to positively impact the host’s immune system, by enhancing T-cell lymphocyte proliferation and activity of natural killer cells, increasing levels of pro-inflammatory cytokines, and thereby restoring deficient responses in immunosuppressed patients. At the same time, it has been shown that it can affect viral RNA levels and hence inhibit growth of several viruses. Due to its immunomodulatory and antiviral properties, and its safety profile, it has been widely used since 1971 against viral infections and diseases, among which subacute sclerosis panencephalitis, herpes simplex virus, human papilloma virus, human immunodeficiency virus, influenza and acute respiratory infections, cytomegalovirus and Epstein–Barr virus infections. Following an analysis of almost five decades of scientific literature since its original approval, we here summarize in vivo and in vitro studies manifesting the means in which IP impacts the host’s immune system. We also provide a synopsis of therapeutic trials in the majority of which IP was found to have a beneficial effect. Lastly, positive results from limited studies, suggesting the putative future use of IP in new therapeutic indications are briefly described. In order to support use of IP against viral infections apart from those already approved, and to establish its use in clinical practice, further well-designed and executed trials are warranted.

Funding: Ewopharma International.

Wybran J, Appelboom T. Isoprinosine (inosiplex): immunological and clinical effects. Immunomodulation. Boston, MA: Springer; 1984. p. 363–74.CrossRef

Masihi KN. C7 Anti-infective activity of immunomodulators. Principles of immunopharmacology. Basel: Birkhäuser; 2011. p. 411–35.CrossRef

You Y, Wang L, Li Y, Wang Q, Cao S, Tu Y, et al. Multicenter randomized study of inosine pranobex versus acyclovir in the treatment of recurrent herpes labialis and recurrent herpes genitalis in Chinese patients. J Dermatol. 2015;42(6):596–601. https://doi.org/10.1111/1346-8138.12845.CrossRefPubMed

Brzeski M, Madhok R, Hunter JA, Capel HA. Randomised, double blind, placebo controlled trial of inosine pranobex in rheumatoid arthritis. Ann Rheum Dis. 1990;49:293–5.CrossRefPubMedPubMedCentral

Majewska A, Lasek W, Janyst M, Mlynarczyk G. In vitro inhibition of HHV-1 replication by inosine pranobex and interferon-α. Acta Pol Pharm. 2016;73(3):637–44.PubMed

Tobolska S, Terpilowska S, Jaroszewski J, Siwicki AK. Genotoxicity and mutagenicity of inosine pranobex. J Vet Res. 2018;62(2):207–13. https://doi.org/10.2478/jvetres-2018-0030.CrossRefPubMedPubMedCentral

Tobólska S, Terpiłowska S, Jaroszewski J, Siwicki AK. Influence of inosine pranobex on cell viability in normal fibroblasts and liver cancer cells. J Vet Res. 2018;62(2):215–20. https://doi.org/10.2478/jvetres-2018-0031.CrossRefPubMedPubMedCentral

Hadden J, Wybran J, editors. Immunopotentiators II Isoprinosine, NPT 15392 and Azimexone: modulators of lymphocyte and macrophage development and function. Advances in Immunopharmacology: Proceedings of the First International Conference on Immunopharmacology; 1981: Elsevier.

Petrova M, Jelev D, Ivanova A, Krastev Z. Isoprinosine affects serum cytokine levels in healthy adults. J Interferon Cytokine Res. 2010;30(4):223–8. https://doi.org/10.1089/jir.2009.0057.CrossRefPubMed

10.

Lasek W, Janyst M, Wolny R, Zapala L, Bocian K, Drela N. Immunomodulatory effects of inosine pranobex on cytokine production by human lymphocytes. Acta Pharm. 2015;65(2):171–80. https://doi.org/10.1515/acph-2015-0015.CrossRefPubMed

11.

Milano S, Dieli M, Millott S, Miceli MD, Maltese E, Cillari E. Effect of isoprinosine on IL-2, IFN-gamma and IL-4 production in vivo and in vitro. Int J Immunopharmacol. 1991;13(7):1013–8.CrossRefPubMed

12.

Tsang KY, Pan JF, Swanger DL, Fudenberg HH. In vitro restoration of immune responses in aging humans by isoprinosine. Int J Immunopharmacol. 1985;7(2):199–206. https://doi.org/10.1016/0192-0561(85)90027-X.CrossRefPubMed

13.

Tsang KY, Fudenberg HH, Pan JF, Gnagy MJ, Bristow CB. An in vitro study on the effects of isoprinosine on immune responses in cancer patients. Int J Immunopharmacol. 1983;5(6):481–90.CrossRefPubMed

14.

Sabat R, Grutz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010;21(5):331–44. https://doi.org/10.1016/j.cytogfr.2010.09.002.CrossRefPubMed

15.

Ahmed RS, Newman AS, O’Daly J, Duffy S, Grafton G, Brady CA, et al. Inosine acedoben dimepranol promotes an early and sustained increase in the natural killer cell component of circulating lymphocytes: a clinical trial supporting anti-viral indications. Int Immunopharmacol. 2017;42:108–14. https://doi.org/10.1016/j.intimp.2016.11.023.CrossRef

16.

Balestrino C, Montesoro E, Nocera A, Ferrarini M, Hoffman T. Augmentation of human peripheral blood natural killer activity by methisoprinol. J Biol Response Modif. 1983;2(6):577–85.

17.

Diaz-Mitoma F, Turgonyi E, Kumar A, Lim W, Larocque L, Hyde BM. Clinical improvement in chronic fatigue syndrome is associated with enhanced natural killer cell-mediated cytotoxicity: the results of a pilot study with Isoprinosine^®. J Chronic Fatigue Syndr. 2003;11(2):71–95.CrossRef

18.

Bekesi JG, Tsang PH, Wallace JI, Roboz JP. Immunorestorative properties of isoprinosine in the treatment of patients at high risk of developing ARC or AIDS. J Clin Lab Immunol. 1987;24(4):155–61.PubMed

19.

Hersey P, Edwards A. Effect of isoprinosine on natural killer cell activity of blood mononuclear cells in vitro and in vivo. Int J Immunopharmacol. 1984;6(4):315–20.CrossRefPubMed

20.

Ohnishi H, Kosuzume H, Inaba H, Ohkura M, Shimada S, Suzuki Y. The immunomodulatory action of inosiplex in relation to its effects in experimental viral infections. Int J Immunopharmacol. 1983;5(3):181–96.CrossRefPubMed

21.

De Simone C, Ricca D, Sorice F. In vitro influence of methisoprinol on human eosinophils. Int J Immunopharmacol. 1982;4(4):369.CrossRef

22.

Ohnishi H, Kosuzume H, Inaba H, Okura M, Morita Y, Mochizuki H, et al. Mechanism of host defense suppression induced by viral infection: mode of action of inosiplex as an antiviral agent. Infect Immun. 1982;38(1):243–50.PubMedPubMedCentral

23.

Renoux G, Renoux M, Guillaumin J-M. Isoprinosine as an immunopotentiator. J Immunopharmacol. 1979;1(3):337–56.CrossRefPubMed

24.

Morin A, Ballet JJ. A recent overview on in vitro and in vivo immunological activities of methisoprinol. Allergol Immunopathol (Madr). 1982;10(2):109–14.

25.

Gordon P, Brown ER. The antiviral activity of Isoprinosine. Can J Microbiol. 1972;18(9):1463–70. https://doi.org/10.1139/m72-224.CrossRefPubMed

26.

De Simone C, Prohost JW. Prohost modulation of immunity by isoprinosine and NPT 15392. Antibiosis and host immunity. Boston, MA: Springer; 1987. p. 279–90.

27.

Linhares R, Rebello M, Nozawa C. Effect of isoprinosine on rotavirus replication in vitro. Braz J Med Biol Res. 1996;29(2):219–22.PubMed

28.

Licht K, Hartl M, Amman F, Anrather D, Janisiw MP, Jantsch MF. Inosine induces context-dependent recoding and translational stalling. Nucleic Acids Res. 2019;47(1):3–14. https://doi.org/10.1093/nar/gky1163.CrossRefPubMed

29.

Fudenberg HH, Whitten HD. Immunostimulation: synthetic and biological modulators of immunity. Annu Rev Pharmacol Toxicol. 1984;24:147–74. https://doi.org/10.1146/annurev.pa.24.040184.001051.CrossRefPubMed

30.

Ginsberg T, Hadden J. Immunopharmacology of methisoprinol. Immunomodulation. Boston, MA: Springer; 1984. p. 331–48.CrossRef

31.

Campoli-Richards DM, Sorkin EM, Heel RC. Inosine pranobex. Drugs. 1986;32(5):383–424.CrossRefPubMed

32.

Simon LN, Glasky AJ. Isoprinosine: an overview. Cancer Treat Rep. 1978;62(11):1963–9.PubMed

33.

Tsang PH, Sei Y, Bekesi JG. Isoprinosine-induced modulation of T-helper-cell subsets and antigen-presenting monocytes (Leu M3 + Ia +) resulted in improvement of T- and B-lymphocyte functions, in vitro in ARC and AIDS patients. Clin Immunol Immunopathol. 1987;45(2):166–76.CrossRefPubMed

34.

Pompidou A, Delsaux M, Telvi L, Mace B, Coutance F, Falkenrodt A, et al. Isoprinosine and imuthiol, two potentially active compounds in patients with AIDS-related complex symptoms. Cancer Res. 1985;45(9 Supplement):4671s–3s.PubMed

35.

Cillari E, Dieli M, Lo Campo P, Sireci G, Caffarelli A, Maltese E, et al. Protective effect of isoprinosine in genetically susceptible BALB/c mice infected with Leishmania major. Immunology. 1991;74(1):25–30.PubMedPubMedCentral

36.

Janíčková O, Ančicová L, Briestenska K, Mistrikova J. The effect of Isoprinosine treatment on persistent infection of Balb/c mice infected with murine gammaherpesvirus 68. Acta Virol. 2017;61(1):32–8.CrossRefPubMed

37.

Krastev Z, Jelev D, Ivanova R. Isoprinosine induces a rapid lympho-mononuclear response in adult participants. Med Inf. 2015;2(1):80–5.

38.

Corey L, Chiang W, Reeves W, Stamm W, Brewer L, Holmes K. Effect of isoprinosine on the cellular immune response in initial genital herpes virus infection. Clin Res. 1979;27:41A.

39.

Galbraith GM, Thiers BH, Fudenberg HH. An open-label trial of immunomodulation therapy with inosiplex (Isoprinosine) in patients with alopecia totalis and cell-mediated immunodeficiency. J Am Acad Dermatol. 1984;11(2):224–30.CrossRefPubMed

40.

Lowy M, Ledoux-Corbusier M, Achten G, Wybran J. Clinical and immunologic response to Isoprinosine in alopecia areata and alopecia universalis: association with autoantibodies. J Am Acad Dermatol. 1985;12(1):78–84.CrossRefPubMed

41.

Wybran J, Schandené L. Isoprinosine in aphthous stomatitis: clinical improvement associated with enhancement of IL2 production. Int J Immunopharmacol. 1985;7(3):318.CrossRef

42.

Dabrowska-Bernstein B, Stasiak A, Dabrowski M, Pawinska A, Cianciara J, Loch T, et al. Evaluation of the treatment of chronic active hepatitis (HBsAg +) with isoprinosine II Immunological studies. Pol Tyg Lek. 1990;45(16–18):347–51.PubMed

43.

Cianciara J, Laskus T, Gabinska E, Loch T. Isoprinosine in the treatment of chronic active hepatitis type B. Scand J Infect Dis. 1990;22(6):645–8.CrossRefPubMed

44.

Schinazi RF, Cannon DL, Arnold BH, Martino-Saltzman D. Combinations of isoprinosine and 3′-azido-3′-deoxythymidine in lymphocytes infected with human immunodeficiency virus type 1. Antimicrob Agents Chemother. 1988;32(12):1784–7.CrossRefPubMedPubMedCentral

45.

Majewska A, Lasek W, Janyst M, Młynarczyk G. Inhibition of adenovirus multiplication by inosine pranobex and interferon α in vitro. Cent Eur J Immunol. 2015;40(4):395–9. https://doi.org/10.5114/ceji.2015.56960.CrossRefPubMed

46.

Piret J, Boivin G. Resistance of herpes simplex viruses to nucleoside analogues: mechanisms, prevalence, and management. Antimicrob Agents Chemother. 2011;55(2):459–72. https://doi.org/10.1128/AAC.00615-10.CrossRefPubMed

47.

Gupta R, Warren T, Wald A. Genital herpes. Lancet. 2007;370(9605):2127–37. https://doi.org/10.1016/s0140-6736(07)61908-4.CrossRefPubMed

48.

Looker KJ, Magaret AS, May MT, Turner KME, Vickerman P, Gottlieb SL, et al. Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012. PLoS ONE. 2015;10(10):e0140765. https://doi.org/10.1371/journal.pone.0140765.CrossRefPubMedPubMedCentral

49.

Looker KJ, Magaret AS, Turner KME, Vickerman P, Gottlieb SL, Newman LM. Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012. PLoS ONE. 2015;10(1):e114989. https://doi.org/10.1371/journal.pone.0114989.CrossRefPubMedPubMedCentral

50.

Pinninti SG, Kimberlin DW. Neonatal herpes simplex virus infections. Semin Perinatol. 2018;42(3):168–75. https://doi.org/10.1053/j.semperi.2018.02.004.CrossRefPubMed

51.

Mekki M, Eley B, Hardie D. Wilmshurst JM Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Dev Med Child Neurol. 2019. https://doi.org/10.1111/dmcn.14166.CrossRefPubMed

52.

Gutierrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol. 2010;52(10):901–7. https://doi.org/10.1111/j.1469-8749.2010.03717.x.CrossRefPubMed

53.

Tatli B, Ekici B, Ozmen M. Current therapies and future perspectives in subacute sclerosing panencephalitis. Expert Rev Neurother. 2012;12(4):485–92. https://doi.org/10.1586/ern.12.21.CrossRefPubMed

54.

Gadoth N. Subacute sclerosing panencephalitis (SSPE) the story of a vanishing disease. Brain Dev. 2012;34(9):705–11. https://doi.org/10.1016/j.braindev.2011.12.008.CrossRefPubMed

55.

Noetzel MJ, Dodson WE. Progressive CT abnormalities despite clinical improvement in SSPE treated with inosiplex. Ann Neurol. 1983;13(4):457–60. https://doi.org/10.1002/ana.410130416.CrossRefPubMed

56.

Solomon T, Hart CA, Vinjamuri S, Beeching NJ, Malucci C, Humphrey P. Treatment of subacute sclerosing panencephalitis with interferon-alpha, ribavirin, and inosiplex. J Child Neurol. 2002;17(9):703–5. https://doi.org/10.1177/088307380201700911.CrossRefPubMed

57.

Huttenlocher PR, Mattson RH. Isoprinosine in subacute sclerosing panencephalitis. Neurology. 1979;29(6):763–71.CrossRefPubMed

58.

Silverberg R, Brenner T, Abramsky O. Inosiplex in the Treatment of Subacute Sclerosing Panencephalitis. Arch Neurol. 1979;36(6):374–5. https://doi.org/10.1001/archneur.1979.00500420084012.CrossRefPubMed

59.

DuRant RH, Dyken PR, Swift AV. The influence of inosiplex treatment on the neurological disability of patients with subacute sclerosing panencephalitis. J Pediatr. 1982;101(2):288–93.CrossRefPubMed

60.

Haddad FS, Risk WS. Isoprinosine treatment in 18 patients with subacute sclerosing panencephalitis: a controlled study. Ann Neurol. 1980;7(2):185–8. https://doi.org/10.1002/ana.410070216.CrossRefPubMed

61.

Jones C, Huttenlocher P, Dyken P, Jabbour JT, Maxwell K. Inosiplex therapy in subacute sclerosing panencephalitis: a multicentre, non-randomised study in 98 patients. Lancet. 1982;319(8280):1034–7. https://doi.org/10.1016/S0140-6736(82)92097-9.CrossRef

62.

Anlar B, Aydin OF, Guven A, Sonmez FM, Kose G, Herguner O. Retrospective evaluation of interferon-beta treatment in subacute sclerosing panencephalitis. Clin Ther. 2004;26(11):1890–4. https://doi.org/10.1016/j.clinthera.2004.11.002.CrossRefPubMed

63.

Anlar B, Yalaz K, Kose G, Saygi S. Beta-interferon plus inosiplex in the treatment of subacute sclerosing panencephalitis. J Child Neurol. 1998;13(11):557–9. https://doi.org/10.1177/088307389801301106.CrossRefPubMed

64.

Fukuyama Y, Nihei K, Matsumoto S, Ebina T, Kamoshita S, Sato T, et al. Clinical effects of MND-19 (Inosiplex) on subacute sclerosing panencephalitis—a multi-institutional collaborative study—the Inosiplex-SSPE Research Committee. Brain Dev. 1987;9(3):270–82.CrossRefPubMed

65.

Nasirian A, Ashrafi M, Nasrabady SE. Use of A-interferon, amantadin and isoprinosine in subacute sclerosing panencephalitis (sspe): comparing the effectiveness. Iran J Child Neurol. 2008;2(2):27–32.

66.

Sobczyk W, Kulczycki J, Piłkowska E, Iwińska B, Milewska D, Szmigielski S. Comparison of the results of the treatment of patients with SSPE using various immunomodulating preparations. Neurol Neurochir Pol. 1991;25(5):626–33.PubMed

67.

Aydin ÖF, Şenbil N, Kuyucu N, Gürer YKY. Combined treatment with subcutaneous interferon-α, oral isoprinosine, and lamivudine for subacute sclerosing panencephalitis. J Child Neurol. 2003;18(2):104–8. https://doi.org/10.1177/08830738030180020701.CrossRefPubMed

68.

Häusler M, Aksoy A, Alber M, Altunbasak S, Angay A, Arsene OT, et al. A multinational survey on actual diagnostics and treatment of subacute sclerosing panencephalitis. Neuropediatrics. 2015;46(6):377–84.CrossRefPubMed

69.

Rafique A, Amjad N, Chand P, Zaidi SSZ, Rana MS, Ahmed K, et al. Subacute sclerosing panencephalitis: clinical and demographic characteristics. J Coll Physicians Surg Pak. 2014;24(8):557–60.PubMed

70.

Mohanty CK, Scott SC. Immunotherapy of genital warts with inosine pranobex (Imunovir): preliminary study. Genitourin Med. 1986;62:352–5. https://doi.org/10.1136/sti.62.5.352.CrossRefPubMedPubMedCentral

71.

Sadoul G, Beuret T. Treatment of cervical and vulvar condylomata by CO2 laser also with a immunostimulant. Rev Fr Gynecol Obstet. 1984;79(11):681–4.PubMed

72.

Davidson-Parker J, Dinsmore W, Khan MH, Hicks DA, Morris CA, Morris DF. Immunotherapy of genital warts with inosine pranobex and conventional treatment: double blind placebo controlled study. Genitourin Med. 1988;64(6):383–6.PubMedPubMedCentral

73.

Tay SK. Efficacy of inosine pranobex oral therapy in subclinical human papillomavirus infection of the vulva: a randomized double-blinded placebo controlled study. Int J STD AIDS. 1996;7(4):276–80. https://doi.org/10.1258/0956462961917960.CrossRefPubMed

74.

Sand-Petersen C, Weismann K. Isoprenosine improves symptoms in young females with chronic vulvodynia. Acta Derm Venereol. 1996;76(5):404.PubMed

75.

Kedrova AG, Podisov YI, Kuznetsov VV, Bryugzin VV, Kozachenko VP, Nikogosyan SO. Role of antiviral therapy in the complex treatment of patients with epithelial dysplasias and preinvasive cancer of the cervix uteri. Akush Ginekol. 2006;6:27–30.

76.

Georgala S, Katoulis A, Befon A, Georgala C, Rigopoulos D. Short communication: oral inosiplex in the treatment of cervical condylomata acuminata: a randomised placebo-controlled trial. BJOG. 2006;113(9):1088–91. https://doi.org/10.1111/j.1471-0528.2006.01041.x.CrossRefPubMed

77.

Femiano F, Gombos F, Scully C. Oral proliferative verrucous leukoplakia (PVL); open trial of surgery compared with combined therapy using surgery and methisoprinol in papillomavirus-related PVL. Int J Oral Maxillofac Surg. 2001;30(4):318–22. https://doi.org/10.1054/ijom.2001.0066.CrossRefPubMed

78.

Pachuta DM, Togo Y, Hornick RB, Schwarts AR, Tominaga S. Evaluation of isoprinosine in experimental human rhinovirus infection. Antimicrob Agents Chemother. 1974;5(4):403–8.CrossRefPubMedPubMedCentral

79.

Waldman RH, Ganguly R. Therapeutic efficacy of inosiplex (Isoprinosine^®) in rhinovirus infection. Ann N Y Acad Sci. 1977;284(1):153–60.CrossRefPubMed

80.

Khakoo RA, Watson GW, Waldman RH, Ganguly R. Effect of inosiplex (isoprinosine) on induced human influenza A infection. J Antimicrob Chemother. 1981;7(4):389–97.CrossRefPubMed

81.

Beran J, Šalapová E, Špajdel M. Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a phase 4, randomised, placebo-controlled, double-blind study. BMC Infect Dis. 2016;16(1):648.CrossRefPubMedPubMedCentral

82.

Lam KC, Lin HJ, Lai CL, Lam SK, Kwan YL. Isoprinosine in classical acute viral hepatitis. Am J Dig Dis. 1978;23(10):893–6.CrossRefPubMed

83.

Scasso A, Paladini A, Della Santa M. Methisoprinol in the treatment of acute B viral hepatitis: controlled clinical study. BMC Infect Dis. 1983;34(3):423–35.

84.

Nikolova N, Antonov K, Mateva L. Krastev Z Could Inosine pranobex and ribavirin in combination restore immune competence in chronic HCV advanced liver disease? MedInform. 2014;1:35–44. https://doi.org/10.18044/medinform.201411.35.CrossRef

85.

Pardo M, Carreño V. Lack of efficacy of inosine pranobex in the treatment of chronic hepatitis C. J Hepatol. 1994;21(2):278.CrossRefPubMed

86.

Wallace JI, Bekesi JG. A double-blind clinical trial of the effects of inosine pranobex in immunodepressed patients with prolonged generalized lymphadenopathy. Clin Immunol Immunopathol. 1986;39(1):179–86.CrossRefPubMed

87.

Pedersen C, Sandström E, Petersen CS, Norkrans G, Gerstoft J, Karlsson A, et al. the efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. N Engl J Med. 1990;322(25):1757–63. https://doi.org/10.1056/nejm199006213222501.CrossRefPubMed

88.

Kovacs JA, Powell F, Voeller D, Allegra CJ. Inhibition of Pneumocystis carinii dihydropteroate synthetase by para-acetamidobenzoic acid: possible mechanism of action of isoprinosine in human immunodeficiency virus infection. Antimicrob Agents Chemother. 1993;37(6):1227–31.CrossRefPubMedPubMedCentral

89.

De Simone C, Famularo G, Tzantzoglou S, Moretti S, Jirillo E. Inosine pranobex in the treatment of HIV infection: a review. Int J Immunopharmacol. 1991;13(Suppl 1):19–27.CrossRefPubMed

90.

Georgala S, Katoulis AC, Befon A, Georgala K, Stavropoulos PG. Inosiplex for treatment of alopecia areata: a randomized placebo-controlled study. Acta Derm Venereol. 2006;86(5):422–4.CrossRefPubMed

91.

Wybran J, Famaey JP, Appelboom T. Inosiplex: a novel treatment in rheumatoid arthritis? J Rheumatol. 1981;8(4):643–6.PubMed

92.

Sadowska-Wroblewska M, Wroblewska-Graff T, Werynska-Przybylska J, Rell-Bakalarska M, Kurdybacha J. Isoprinosine in the early pre-erosive stage of rheumatoid arthritis: a pilot study. Z Rheumatol. 1988;47(2):113–6.PubMed

93.

Becker H, Loers E, Helmke K, Federlin K. Therapy of rheumatic diseases with inosiplex. Immun Infekt. 1986;14(3):93–9.PubMed

94.

Centers for disease control and prevention. What is ME/CFS? 2018. https://www.cdc.gov/me-cfs/about/index.html. Accessed 15 Feb 2019.

95.

World Health Organization. Atlas: multiple sclerosis resources in the world 2008. Geneva: World Health Organization; 2008.

96.

Hommes OR, Comi G. Early indicators early treatments neuroprotection in multiple sclerosis. Milano: Springer; 2004.CrossRef

97.

Caltagirone C, Carlesimo A. Methisoprinol in the treatment of multiple sclerosis. A pilot study. Acta Neurol Scand. 1986;74(4):293–6.CrossRefPubMed

98.

Mazzarello P, Rocchelli B, Poloni M, Delodovici M, Pinelli P. Isoprinosine in multiple sclerosis treatment: a preliminary study. Schweiz Arch Neurol Neurochir Psychiatr. 1982;131(2):175–9.PubMed

99.

Pompidou A, Rancurel G, Delsaux M, Meunier C, Telvi L, Cour V, et al. Immunosuppressive effects of isoprinosine in man: a comparison to chlorambucil effects in multiple sclerosis. Cancer Detect Prev Suppl. 1987;1:377–83.PubMed

100.

Milligan NM, Miller DH, Compston DA. A placebo-controlled trial of isoprinosine in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 1994;57(2):164–8.CrossRefPubMedPubMedCentral

101.

World Health Organization. Global tuberculosis report 2018. 2018.

102.

Laurenzi M, Ginsberg A, Spigelman M. Challenges associated with current and future TB treatment. Curr Drug Targets Infect Disord. 2007;7(2):105–19.CrossRef

103.

Mishra AK, Yabaji SM, Dubey RK. Evaluation of isoprinosine to be repurposed as an adjunct anti-tuberculosis chemotherapy. Med Hypotheses. 2018;115:77–80. https://doi.org/10.1016/j.mehy.2018.04.002.CrossRefPubMed

104.

Ompico MG. Methisoprinol for children with early phase dengue infection: a pilot study. Paediatr Indones. 2013;53(6):320–7.CrossRef

105.

Sarciron ME, Delabre I, Walbaum S, Raynaud G, Petavy AF. Effects of multiple doses of isoprinosine on Echinococcus multilocularis metacestodes. Antimicrob Agents Chemother. 1992;36(1):191–4. https://doi.org/10.1128/aac.36.1.191.CrossRefPubMedPubMedCentral

106.

Sarciron ME, Walbaum S. Petavy AF Effects of Isoprinosine on Echinococcus multilocularis and E. granulosus metacestodes. Parasitol Res. 1995;81(4):329–33. https://doi.org/10.1007/bf00931540.CrossRefPubMed

107.

Lawton P, Walchshofer N, Sarciron M. In vitro effects of isoprinosine and a dipeptide methyl ester on Echinococcus multilocularis protoscoleces. J Helminthol. 2001;75(3):251–7.PubMed

108.

Gascon GG. Randomized treatment study of inosiplex versus combined inosiplex and intraventricular interferon-α in subacute sclerosing panencephalitis (SSPE): international multicenter study. J Child Neurol. 2003;18(12):819–27.CrossRefPubMed

109.

Nakamura T, Miyasaka N, Pope RM, Talal N, Russell IJ. Immunomodulation by isoprinosine: effects on in vitro immune functions of lymphocytes from humans with autoimmune diseases. Clin Exp Immunol. 1983;52(1):67–74.PubMedPubMedCentral

110.

Wiranowska-Stewart M, Hadden JW. Effects of isoprinosine and NPT 15392 on interleukin-2 (IL-2) production. Int J Immunopharmacol. 1986;8(1):63–9.CrossRefPubMed

111.

Tsang KY, Donnelly R, Galbraith G, Fudenberg HH. Isoprinosine effects on interleukin-1 production in acquired immune deficiency syndrome (AIDS). Int J Immunopharmacol. 1986;8(4):437–41.CrossRefPubMed

112.

Tsang KY, Fudenberg H, Galbraith G, Donnelly R, Bishop L, Koopmann W. Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro. J Clin Invest. 1985;75(5):1538–44.CrossRefPubMedPubMedCentral

113.

Silvennoinen-Kassinen S, Karttunen R, Tiilikainen A, Huttunen K. Isoprinosine enhances PHA responses and has potential effect on natural killer cell (NK) activity of uremic patients in vitro. Nephron. 1987;46(3):243–6. https://doi.org/10.1159/000184362.CrossRefPubMed

114.

Hersey P, Bindon C, Bradley M, Hasic E. Effect of isoprinosine on interleukin 1 and 2 production and on suppressor cell activity in pokeweed mitogen stimulated cultures of B and T cells. Int J Immunopharmacol. 1984;6(4):321–8.CrossRefPubMed

115.

De Simone C, Capozzi C, Campo S, Ricca D, Matteucci G. Effect of azathioprine and inosiplex on rosette formation by lymphocytes from normal donors and from patients with neoplasia. Ann Sclavo. 1981;23:116–24.PubMed

116.

Galli M, Lazzarin A, Moroni M, Zanussi C. Inosiplex in recurrent herpes simplex infections. Lancet. 1982;320(8293):331–2.CrossRef

117.

Galli M, Lazzarin A, Moroni M, Zanussi C. Treatment of recurrent viral infectious diseases by methisoprinol. In: Fudenberg HH, Whitten HD, Ambrogi F, editors. Immunomodulation: new frontiers and advances. Boston: Springer; 1984. p. 385–97.CrossRef

118.

Talbot DJ, Menday AP, Saurat JH. Inosine pranobex in mucocutaneous herpes. Lancet. 1985;325(8433):877. https://doi.org/10.1016/S0140-6736(85)92239-1.CrossRef

119.

Cutler J, Talbot DJ. The successful treatment of Herpes genitalis with Imunovir (inosine pranobex) 6th International Meeting of the International Society for STD Research; 31st July–2nd August 1985. England: Brighton; 1985.

120.

Byrne M, Lawrence A, Walker G, O’Neill O, Csonka G, John J. Suppression of recurrent genital herpes by inosine pranobex: effects of episodic and continuous treatment. BMC Infect Dis. 1988;43(4):681–8.

121.

Mindel A, Carney O, Sonnex C, Freris M, Patou G, Williams P. Suppression of frequently recurring genital herpes: acyclovir v inosine pranobex. Sex Transm Infect. 1989;65(2):103–5.CrossRef

122.

Kinghorn G, Woolley P, Thin R, De Maubeuge J, Foidart J-M, Engst R. Acyclovir vs. isoprinosine (immunovir) for suppression of recurrent genital herpes simplex infection. Sex Transm Infect. 1992;68(5):312–6.CrossRef

123.

Feldman S, Hayes FA, Chaudhary S, Ossi M. Inosiplex for localized herpes zoster in childhood cancer patients: preliminary controlled study. Antimicrob Agents Chemother. 1978;14(3):495–7.CrossRefPubMedPubMedCentral

124.

Lesourd B, Laude J, Meunier P, Doumerc S, Moulias R. Isoprinosine treatment of herpes zoster. Results of a control study in 36 subjects. Nouv Presse Med. 1982;11(3):191–3.PubMed

125.

Castelli M, Zanca A, Giubertoni G, Zanca A, Bertolini A. Griseofulvin-methisoprinol combination in the treatment of herpes zoster. Pharmacol Res Commun. 1986;18(10):991–6.CrossRefPubMed

126.

Payne CMR, Menday AP, Rogers T, Staughton RC. Isoprinosine does not influence the natural history of herpes zoster or postherpetic neuralgia. Scand J Infect Dis. 1989;21(1):15–8.CrossRefPubMed

127.

Yalaz K, Anlar B, Oktem F, Aysun S, Ustacelebi S, Gurcay O, et al. Intraventricular interferon and oral inosiplex in the treatment of subacute sclerosing panencephalitis. Neurology. 1992;42(3 Pt 1):488–91.CrossRefPubMed

128.

Gascon G, Yamani S, Crowell J, Stigsby B, Nester M, Kanaan I, et al. Combined oral isoprinosine-intraventricular alpha-interferon therapy for subacute sclerosing panencephalitis. Brain Dev. 1993;15(5):346–55.CrossRefPubMed

129.

Anlar B, Yalaz K, Oktem F, Kose G. Long-term follow-up of patients with subacute sclerosing panencephalitis treated with intraventricular alpha-interferon. Neurology. 1997;48(2):526–8.CrossRefPubMed

130.

Gokcil Z, Odabasi Z, Demirkaya S, Eroglu E, Vural O. Alpha-interferon and isoprinosine in adult-onset subacute sclerosing panencephalitis. J Neurol Sci. 1999;162(1):62–4.CrossRefPubMed

131.

Eroglu E, Gokcil Z, Bek S, Ulas UH, Ozdag MF, Odabasi Z. Long-term follow-up of patients with adult-onset subacute sclerosing panencephalitis. J Neurol Sci. 2008;275(1–2):113–6.CrossRefPubMed

132.

Zagni G, Cannarozzo C. Clinical trial on the topical application of methisoprinol in some cutaneous viruses. Clin Eur. 1982;21:3–7.

133.

Malgouyat J. A new approach to the treatment of genital condyloma in women. Gynecologie. 1983;34(5):415–517.

134.

Mihula M. Possible treatment of anogenital warts with the immunomodulation agent Isoprinosine. Prakt Gyn. 2015;19(2):101–6.

135.

Nejmark B, Kondrat’eva J, Zologina V, Torbik D. Effectiveness of combined treatment of HPV infection. Urologiia. 2015;2:39–40.

Title: Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases
Authors: Jiri Sliva
Chrysoula N. Pantzartzi
Martin Votava
Publication date: 01-08-2019
Publisher: Springer Healthcare
Keywords: Herpes Virus
Influenza
Published in: Advances in Therapy / Issue 8/2019
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI: https://doi.org/10.1007/s12325-019-00995-6

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Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases

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Abstract

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