Prohost Modulation of Immunity by Isoprinosine and NPT 15392

  • Claudio DeSimone
  • John W. Hadden


Antimicrobial agents which act on nucleic acids (e.g., rifampin, sulfonamides, trimethoprim, metronidazole), on ribosomes (e.g., tetracyclines, chloramphenicol, aminoglycosides) or on cytoplasmic membranes (e.g., amphotericin B, griseofulvin, polymyxin, imidazoles) positively influence the outcome of infections by acting against the offending pathogens but they may also have negative effects on the host’s immunocompetence (22). Although the immunosuppressive properties of most of the antimicrobials are not sufficient to warrant restricting their use, under certain circumstances a “pro-host” immunopharmacological approach seems warranted. In this regard it is important to remember that the immune system “cures” an infection, not the antimicrobial agent, and under circumstances where antimicrobial therapy is lifesaving, the host’s immune defenses are almost invariably compromised. To expedite the development of immunorestorative therapy it is important first of all to characterize the immunological deficiency which precedes, accompanies or follows a disease in order to select the appropriate immunorestorative agent. Secondly, new therapeutic strategies, where the antimicrobials are associated with prohost immunomodulating drugs, need to be studied in the appropriate animal systems.


Herpes Simplex Herpes Zoster Natural Killer Cell Activity Condyloma Acuminatum Genital Herpes 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. Azzara, A. Meozzi, G. Carulli, M. Martelli, F. Tangheroni, E. Serravalle and F. Ambrogi, Normalizzazione di funzioni neutrofiliche in bambini affetti da infezioni croniche ricorrenti dopo terapia ciclica con metisoprinolo, Chemioterapia 3:179 (1983).Google Scholar
  2. 2.
    C. Balestrino, E. Montesoro, A. Nocera, M. Ferrarini and T. Hoffman, Incremento dell’ attivita NK di cellule mononucleate di sangue periferico umano dopo trattamento con metisoprinolo, Biol. Resp. Modifiers 2:577 (1983).Google Scholar
  3. 3.
    M. Bechi and A. Cini, L’impiego del metisoprinolo nel trattamento della epatite virale acuta, Clin. Europea. 20:79 (1981).Google Scholar
  4. 4.
    R. F. Betts, R. G. Douglas, S. D. George and C. J. Rinehart, Isoprinosine in experimental influenza A infection in volunteers, 78th Annual Meeting of A.S.M., Las Vegas, Nevada (1978).Google Scholar
  5. 5.
    L. J. Bradshaw, H. L. Sumner, W. H. Wickett, Jr. and E. B. Correia, Immunological and clinical studies on herpes simplex patients treated with inosiplex, 4th International Congress of Immunology, Paris, Abst. 17.7.5 (1980).Google Scholar
  6. 6.
    S. Catania, F. Zennaro, P. Vittucci and M. Monacelli, Indagine clinica sul trattamento della varicella con isoprinosina, G. Mal. Inf. 35:194 (1983).Google Scholar
  7. 7.
    I. Cerutti, C. Chany and J. F. Schlumberger, Isoprinosine increases the antitumor action of interferon, Int. J. Immunopharmacol. 1:59 (1979).PubMedCrossRefGoogle Scholar
  8. 8.
    T. W. Chang and L. Weinstein, Antiviral activity of isoprinosine in vitro and in vivo, Am. J. Med. Sci. 265:143 (1973).PubMedCrossRefGoogle Scholar
  9. 9.
    P. Cornaglia-Ferraris, R. Coffey and J. W. Hadden, Purine substituted analogs as immunomodulators, EOS 4:134 (1984).Google Scholar
  10. 10.
    M. Danto, R. Colella, G. Borrelli, G. LaBella and R. Mele, L’uso di metisoprinolo in corso di broncopeumopatie croniche riacutizzate, Clin. Europea. 20:130 (1981).Google Scholar
  11. 11.
    M. D’Aquino, A. Borri, E. Radin, S. Scremin and L. Caprioglio, Efficacia del metisoprinolo nella terapia delle epatiti acute virali, 11th Congr. Naz. A.M.O.I., G. Mal. Infett. 34:1746 (1982).Google Scholar
  12. 12.
    S. W. D’Arca, A. Pana and M. Grassi, Attivita del metisoprinolo nei confronti del virus rabbico: Valutazione in vitro, EOS 3:8 (1983).Google Scholar
  13. 13.
    G. Delogu, D. Meli, C. DeSimone, G. Cristina, A. Lozzi and G. DeRitis, Impiego del metisoprinolo in un caso di poliradicolonevrite virale a prevalente incidenza bulbare, XI Congresso Nazionale A.M.O.I., Napoli giugno (1981).Google Scholar
  14. 14.
    C. DeSimone, G. W. Canonica, G. Corte and D. Meli, Influence of methisoprinol on surface antigens of T lymphocytes, Curr. Chemother. Immunother. 1:1161 (1982).Google Scholar
  15. 15.
    C. DeSimone, C. Capozzi, S. Campo, D. Ricca and G. Matteucci, Effetto dell’ azatioprina e dell’ inosiplex sulla formazione di rosette da parte dei linfociti di soggetti sani e di pazienti con neoplasie, Ann. Sclavo. 23:116 (1981).Google Scholar
  16. 16.
    C. DeSimone, A. Cilli, S. Zanzoglu and F. Matricardi, Results of clinical trials with methisoprinol in Italy, EOS 4:108 (1984).Google Scholar
  17. 17.
    C. DeSimone, G. Delogu, L. Pugnaloni and C. Mastropietro, Methisoprinol and corticosteroids: Immunopharmacokinetic assessment, Tissue Reactions 1:101 (1984).Google Scholar
  18. 18.
    C. DeSimone, A. Koverech, L. Pugnaloni, C. Mastropietro, M. C. Salis and F. Sorice, Defective adenosine-inducible suppressor T lympho-cyte generation by NPT 15392 and methisoprinol, Int. J. Immunother. 1:67 (1985).Google Scholar
  19. 19.
    C. DeSimone, D. Meli, M. Sbricoli, E. Rebuzzi and A. Koverech, In vitro effect of inosiplex on T lymphocytes: Influence on T cells with receptors for IgG (Ty), Int. J. Immunopharmacol. 4:139 (1982).Google Scholar
  20. 20.
    C. DeSimone, L. Pugnaloni, S. DeSantis, L. Baldinelli and F. Sorice, Influence of methisoprinol on kinetics of immune interferon production and blastogenesis, Int. J. Immunopharmacol. 3:317 (1985).CrossRefGoogle Scholar
  21. 21.
    C. DeSimone, A. Ricca, A. Lozzi and L. Lucci, Influence of methisoprinol on 0KT4+, 0KT8+, 0KM1+, 0KIal+ cells, Int. J. Immuno-pharmacol. 4:291 (1982).CrossRefGoogle Scholar
  22. 22.
    R. Finch, Immunomodulating effects of antimicrobial agents, J.Antimicrobiol. Chemother. 6:691 (1980).CrossRefGoogle Scholar
  23. 23.
    I. Florentin, M. Bruley-Rosset, J. Schulz, M. Davigny, N. Kiger and G.Mathe, Attempt at functional classification of chemically-defined immunomodulators, in: “Advances in Immunopharmacology,” J. W. Hadden, L. Chedid, P. Mullen and F. Spreafico, eds., Pergamon Press, Oxford (1981).Google Scholar
  24. 24.
    I. Florentin, E. Taylor, M. Davigny, C. Mathe and J. W. Hadden, Kinetic studies of the immunopharmacologic effects of NPT 15392 in mice, Int. J. Immunopharmacol. 4:225 (1982).PubMedCrossRefGoogle Scholar
  25. 25.
    V. Frappamaina, L. Monno, F. Trotta and G. Pastore, Clearance sierica dell ’HB e AG nell ’epatite acuta di tipo B trattata con metiso-prinolo, EOS 2:115 (1982).Google Scholar
  26. 26.
    H. Friedman, R. Calle and A. Morin, Double-blind study of isoprinosine influence on immune parameters in solid tumor-bearing patients treated by radiotherapy, Int. J. Immunopharmacol. 2:194 (1980).CrossRefGoogle Scholar
  27. 27.
    M. Galli, A. Lazzarin, M. Moroni and C. Zanussi, Inosiplex in recurrent herpes simplex infections, Lancet 2:331 (1982).PubMedCrossRefGoogle Scholar
  28. 28.
    T. Ginsberg, Urinary excretion of purine metabolites in macaca mulatta following administration of inosine and l-(dimethylamino)-2-pro-panol, p acetamidobenzoate, 5th Congress Pharmacology, S. Francisco, CA (1972).Google Scholar
  29. 29.
    T. Ginsberg and A. J. Glasky, Inosiplex: an immunomodulation model for the treatment of viral disease, Third conference on antiviral substances, Ann. N. Y. Acad. Sci. 284:128 (1977).PubMedCrossRefGoogle Scholar
  30. 30.
    A. J. Glasky, G. E. Friebertshauser, J. W. Halker, R. A. Settineri and T. Ginsberg, The role of cell mediated immunity in the therapeutic action of viral disease processes, Chemotherapy 6:235 (1976).Google Scholar
  31. 31.
    A. Glasky, J. Gordon, F. Hoehler, J. Wallace and J. C. Bekesi, Isoprinosine (INPX) in progressive generalized lymphodenopathy (PGC) -kinetics of action and clinical response, Int. J. Immunopharmacol. 7:318 (1985).CrossRefGoogle Scholar
  32. 32.
    P. Gordon and E. R. Brown, The antiviral activity of isoprinosine,Can. J. Microbiol. 18:1463 (1972).PubMedCrossRefGoogle Scholar
  33. 33.
    P. Gordon, B. Ronsen and E. R. Brown, Anti-herpes virus action of isoprinosine, Antimicrob. Agents Chemother. 5:153 (1974).PubMedGoogle Scholar
  34. 34.
    P. Gordon and B. Rosen, Isoprinosine: biochemical correlates of antiviral and experimental learning-enhancing activities, FASEB 29:684 (1970).Google Scholar
  35. 35.
    A. Goutner, In vitro modulation of natural killer cell activity by isoprinosine, NPT 15392, and interferon, Int. J. Immunopharmacol. 2:197 (1980).CrossRefGoogle Scholar
  36. 36.
    G. Grippaudo, V. Diminiello and G. Fratto, Il metisoprinolo nel trattamento delle manifestazioni erpetiche intra ed extra-orali, Inform. Sanitario 4:1 (1982).Google Scholar
  37. 37.
    J. W. Hadden, P. Cornaglia-Ferraris and R. Coffey, Purine analogs as immunomodulators, in: “Progress in Immunology,” Academic Press, Japan (1984).Google Scholar
  38. 38.
    J. W. Hadden and A. Giner-Sorolla, Isoprinosine and NPT 15392: Modulators of lymphocyte and macrophage development and function, in: “Augmenting Agents in Cancer Therapy: Current Status and Future Perspectives,” M. Chirigos and E. Hersh, eds., Raven Press, New York (1980).Google Scholar
  39. 39.
    J. W. Hadden and A. Giner-Sorolla, Isoprinosine and NPT 15392:Modulators of lymphocyte and macrophage development and function, Prog. Cancer Res. Ther. 16:492 (1981).Google Scholar
  40. 40.
    J. W. Hadden, A. Giner-Sorolla, E. M. Hadden, S. Ikehara, R. Pahwa, R. Coffey, A. M. Castellazi, C. Jones, K. Maxwell and L. Simon, NPT 16416: A levamisole-like purine with immunomodulatory effects, Int. J. Immunopharmacol. Abst. 4:287 (1982).CrossRefGoogle Scholar
  41. 41.
    J. W. Hadden, E. M. Hadden and R. G. Coffey, Isoprinosine augmentation of phytohemagglutinin induced lymphocyte proliferation, Infect. Immun. 13:382 (1976).PubMedGoogle Scholar
  42. 42.
    J. W. Hadden, E. M. Hadden, T. Spira, R. Sedlineri, L. Simon and A.Giner-Sorolla, Effects of NPT 15392 in vitro on human leukocyte functions, Int. J. Immunopharmacol. 4:225 (1982).PubMedCrossRefGoogle Scholar
  43. 43.
    J. W. Hadden, C. Lopez, R. J. O’Reilly and E. M. Hadden, Levamisole and inosiplex: Antiviral agents with immunopotentiating action, Third Conference on Antiviral Substances, Ann. N. Y. Acad. Sci. 284:139 (1977).PubMedCrossRefGoogle Scholar
  44. 44.
    P. Hersey, C. Bindon, M. Bradley and E. Hasic, 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. 6:315 (1984).PubMedCrossRefGoogle Scholar
  45. 45.
    S. Ikehara, J. W. Hadden, R. A. Good and R. Pahwa, In vitro effects of two immunopotentiators, isoprinosine and NPT 15392, on murine T cells differentiation and function, Thymus 3:90 (1981).Google Scholar
  46. 46.
    G. Italia and E. Rizza, Studio clinico sull’ impiego del metisoprinolo nell’ herpes genitalis, Quad. Clin. Ostetrica Ginecologia 37:129 (1982).Google Scholar
  47. 47.
    C. E. Jones, P. R. Dyken, P. R. Hutteniocher, J. T. Jabbour and K. W. Maxwell, Inosiplex therapy in subacute sclerosing panencephalitis: A multicentre non-randomised study in 98, Lancet 1:1034 (1982).PubMedCrossRefGoogle Scholar
  48. 48.
    F. G. Lento, S. Tandurella, C. Baretti, G. Cannata and R. Salerno, Pazienti affetti da herpes zoster trattati con metisoprinolo, G. Ital. Pat. 28:9 (1983).Google Scholar
  49. 49.
    F. Loiacono, D. Agnello, R. Malizia and M. Balsamo. Il metisoprinolo nel trattamento di alcune affezioni delle vie respiratorie del bambino, Aggior. Pediat. 33:85 (1982).Google Scholar
  50. 50.
    S. Longley, R. L. Dunning and R. H. Waldman, Effect of isoprinosine against challenge with A(H3N2)/Hong Kong influence virus in volunteers, Antimicrob. Agents Chemother. 3:506 (1973).PubMedGoogle Scholar
  51. 51.
    V. J. Merluzzi, M. M. Walker, N. Williams, B. Susskind, J. W. Hadden and R. Faanes, Immunoenhancing activity of NPT 15392: A potential immune response modifier, Int. J. Immunopharmacol. 4:219 (1982).PubMedCrossRefGoogle Scholar
  52. 52.
    A. Miglietta, M. T. Ventura, F. Dammacco and L. Bonomo, Effetto del metisoprinolo sulla fagocitosi dei monociti e dei granulociti neutrofili in vitro, EOS 2:13 (1981).Google Scholar
  53. 53.
    G. Migneco, C. LaCascia, S. Mansueto and S. Tripi, Analisi e valutazione delle modificazioni del quadro clinico di epatiti croniche in corso di trattamento con metisoprinolo, Riv. Parassitologia 43:331 (1981).Google Scholar
  54. 54.
    A. Morin, C. Griscelli and F. Daguillard, Effets de l’ isoprinosine sur l’ activation des lymphocytes humains in vitro, Ann. Immunol. 130:541 (1979).Google Scholar
  55. 55.
    A. Morin, J. L. Touraine, G. Renoux and J. W. Hadden, Isoprinosine as an immunomodulating agent, in: “International Symposium on New Trends in Human Cancer, Immunology and Cancer Immunotherapy,” B. Serrou and C. Rosenfeld, eds., Doin Editeur, Paris (1980).Google Scholar
  56. 56.
    H. Ohnishi, H. Kosuzume, I. Hitoshi, O. Masatsugu, Y. Morita, H. Mochizuki and Y. Zusuki, Mechanism of host defense suppression induced by viral infection: Mode of action of inosiplex as an antiviral agent, Infec. Immun. 243:38 (1982).Google Scholar
  57. 57.
    H. Ohnishi, H. Kosuzume, H. Inaba, M. Okura, S. Shimada, H. Tajima and Y. Suzuki, The immunomodulatory action of inosiplex in relation to its effects in experimental viral infections, Int. J. Immunopharmacol. 5:181 (1983).PubMedCrossRefGoogle Scholar
  58. 58.
    D. M. Pachuta, Y. Togo, R. B. Hornick, A. R. Schwartz and S. Tominaga,Evaluation of isoprinosine in experimental human rhinovirus infection, Antimicrob. Agents Chemother. 5:403 (1974).PubMedGoogle Scholar
  59. 59.
    A. Paffetti, D. Curti, V. Renda, A. Nurzia and S. Carlizzi, II metisoprinolo nella epatite acuta virale di tipo B, Riv. Sci. Med. Farmacol. 5:361 (1983).Google Scholar
  60. 60.
    E. Pasqui, A. Alzeni, G. Verrocchi, G. Daga and A. Carta, Terapia con metisoprinolo di 50 casi di epatite virale acuta, Riv. Pat. Clin. 35:735 (1980).Google Scholar
  61. 61.
    A. Polloni, M. Carrai, A. Capria and G. Corsini, Trattamento delle epatiti croniche HB Ag positive con metisoprinolo: Prime esperienze, Riv. Gastroent. 33:41 (1981).Google Scholar
  62. 62.
    A. Pompidou, In vitro effects of methisoprinol on human peripheral blood lymphocytes, EOS 4:112 (1984).Google Scholar
  63. 63.
    G. Precchia, M. Del Vecchio, G. Morelli, P. Tarallo, C. Ciccarello, A. Precchia and P. Amoroso, Il metisoprinolo nella terapia delle malattie viral: dati preliminari sul trattamento di un gruppo di malattie, Chemioter. Antimicrobican. 4:64 (1981).Google Scholar
  64. 64.
    G. Rancurel and A. Buge, Bull. et Mem. Soc. Med. Paris IX:49 (1981).Google Scholar
  65. 65.
    G. Rancurel, B. Lesourd, A. Pompidou, D. Denvil, C. Pontes, R. Moulias and A. Buge, Immunological status in necrotic acute encephalitis (NAW), L’infection herpetique humaine et ses traitments, Facultè de Medicine de Brest, Proceedings (1981).Google Scholar
  66. 66.
    G. Renoux, M. Renoux and D. Degenne, Suppressor cell activity after isoprinosine treatment of lymphocytes from normal mice, Int. J. Immunopharmacol. 1:239 (1979).PubMedCrossRefGoogle Scholar
  67. 67.
    G. Renoux, M. Renoux, J. M. Guillaumin and C. Gouzien, Differentiation and regulation of lymphocyte populations -evidence for immunopoten-tiation induced T cell recruitment, Int. J. Immunopharmacol. 1:415 (1979).Google Scholar
  68. 68.
    G. Santangelo, S. Lombardo, S. Randazzo, N. Maccarone and M. Amato, Il Virtixan nelle infezioni virali dell’ infanzia: Prospettive terapeutiche nelle infezioni virali ricorrenti dell’ eta del lattante, Aggior. Pediatr. 32:1 (1981).Google Scholar
  69. 69.
    A. J. Sato, T. S. Hall and S. E. Reed, Trial of the antiviral action of isoprinosine against rhinovirus infection of volunteers, Antimicrob. Agents Chemother. 3:332 (1973).Google Scholar
  70. 70.
    I. Signorelli, G. Garbarino and S. Tampucci, Studio clinico del metisoprinolo in pazienti affette da condiloma acuminato, G. Ital. Ostet. Ginecol. 4:11 (1982).Google Scholar
  71. 71.
    L. N. Simon and A. J. Glasky, Isoprinosine: an overview, Cancer Treatment Reports 62:1963 (1978).PubMedGoogle Scholar
  72. 72.
    L. N. Simon, F. K. Hoehler, T. Ginsberg and J. W. Hadden, NPT 15392:A new chemically defined biological response modifier, in: “Immune Modulation Agents and Their Actions,” E. Fenichel and M. A. Chirigos, eds., Marcel Dekker, Inc., New York, N.Y. (1984).Google Scholar
  73. 73.
    A. Sinardi, L. Santamaria, C. Practico, L. Siracusano and A. Martino, Su due casi di meningo-encefalite virale trattati con metisoprinolo, Clin. Europa. 22:396 (1983).Google Scholar
  74. 74.
    S. Spadafora, Il metisoprinolo in alcune virosi cutanee; nostre prime esperienze, Esp. Med. Chir. 1:83 (1981).Google Scholar
  75. 75.
    S. Specter and J. W. Hadden, Thymomimetic drugs, in: “Immunomodulation,” J. W. Hadden and F. Spreafico, eds., Springer Verlag, in press (1985).Google Scholar
  76. 76.
    J-L. Touraine, J. W. Hadden and F. Touraine, Isoprinosine-induced T cell differentiation and T cell suppressor activity in humans, in: “Current Chemotherapy and Infectious Disease,” J. D. Nelson and C. Grassi, eds., A.S.M., Washington, D.C. (1980).Google Scholar
  77. 77.
    J. L. Touraine, B. Serrou, J. W. Hadden, A. Morin and F. Touraine, Modulation of suppressor T cell activity by isoprinosine, in: “International Symposium on New Trends in Human Immunology and Cancer Immunotherapy,” G. Serrou and C. Rosenfeld, eds., Doin, Paris (1980).Google Scholar
  78. 78.
    S. Tripi, G. Migneco and C. LaCascia, Comportamento dell’ antigene di superficile del virus dell’ epatite B(HB Ag) e del suo anticorpo (HB Ab) in pazienti con epatite acuta trittati con metisoprinolo, Riv. Parassit. 42:345 (1981).Google Scholar
  79. 79.
    K. Y. Tsang, H. H. Fudenberg, G. M. P. Golbriath, R. P. Donnelly, L. R. Bishop and W. R. Koopenen, Partial restoration of interleukin 2 production and tac (putative interleukin 2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment, J. Clin. Invest. 5:1538 (1985).CrossRefGoogle Scholar
  80. 80.
    A. Vellucci, G. Galanti and A. Delongis, Virus epatite acuta trattata con metisoprinolo. Nostre osservazioni preliminari in 22 casi, G. Mal. Infett. 34:611 (1982).Google Scholar
  81. 81.
    G. Villa, C. Caltagirone and G. Macchi, Unusual clinical course in a case of Creutzfeldt-Jakob disease, Ital. J. Neurol. Sci. 2:155 (1982).CrossRefGoogle Scholar
  82. 82.
    R. H. Waldman and R. Ganguly, Therapeutic efficacy of inosiplex (isoprinosine) in rhinovirus infection, Ann. N. Y. Acad. Sci. 284:153 (1977).PubMedCrossRefGoogle Scholar
  83. 83.
    J. Wybran, A. Govaerts and J. Appleboom, Inosiplex, a stimulating agent for normal human T cells and human leukocytes, J. Immunol. 121:1181 (1978).Google Scholar
  84. 84.
    J. Wybran, B. Serrou, D. Belpomme, J. Boneterre, A. Desplaces, R.Favre, T. Ginsberg, J. M. Lang, G. Mayer, D. T. McKenzie, M. Miksche, D. C. Petit, G. Renoux, C. Rosenfeld, M. Schneider, L. N. Simon and L. Toujas, Immnnomodulating of T cell and NK function by NPT 15392 in cancer patients, in: “Current Concepts in Human Immunology and Cancer Immunomodulation,” B. Serrou, G. Rosenfeld, J. C. Daniels and J. P. Saunders, eds., Elsevier Biomedical, Netherlands (1982).Google Scholar
  85. 85.
    G. F. Zagni and C. Cannarozzo, Studio clinico sui metisoprinolo per uso topico in alcune virosi cutanee, Clin. Europea. 21:585 (1982).Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Claudio DeSimone
    • 1
  • John W. Hadden
    • 2
  1. 1.Clinica Malattie InfettivePoliclinico Umberto IRomeItaly
  2. 2.Program of ImmunopharmacologyUniversity of South Florida College of MedicineTampaUSA

Personalised recommendations