Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Modulation of T- and B-lymphocyte functions by isoprinosine in homosexual subjects with prodromata and in patients with acquired immune deficiency syndrome (AIDS)


Male prodromal homosexuals and patients with acquired immune deficiency syndrome (AIDS) exhibited similar immunological abnormalities but by different degrees. A reduction in the number of circulating T lymphocytes bearing the T-4 surface marker led to an altered ratio of Th to Ts subpopulations in both groups of subjects. Total numbers of suppressor cells (Ts) remained virtually similar in both study groups to that of the control subjects. Proliferative responses to T-cell mitogen (PHA) and T cell-dependent B-cell mitogen (PWM) were severely impaired in prodromal subjects and more so in the AIDS group. The response to PWM was unrelated to the total number of suppressor T cells but was associated with a significant decrease in helper T-cell number. The impaired lymphocyte functions of immunosuppressed subjects were potentiated by coincubation with isoprinosine in a selective fashion. While the percentage of upward modulation among homosexuals with normal lymphocyte functions was comparable to that obtained in control subjects, a higher degree of augmentation was achieved in AIDS patients and in prodromal subjects with impaired blastogenic responses. In none of the AIDS patients with severe immunodeficiencies, however, was the lymphocyte functions restored to the normal range established in the heterosexual controls. These results suggest the feasibility of eventual prophylactic utilization of isoprinosine in male homosexuals at high risk of developing AIDS.

This is a preview of subscription content, log in to check access.


  1. 1.

    Vilmer E, Rouzioux C, Fischer A, Chermann JC, Barre-Sinoussi F, Gazengel C, Dauguet C, Manigne P, Griscelli C: Isolation of New Lymphotropic Retrovirus from Two Siblings with Haemophilia B, One with AIDS. Lancet 753–756, 1984

  2. 2.

    Essex M, McLean MF, Lee TH, Falk L, Howe CWS, Mullins JI, Cabradilla C, Francis DP: Antibodies to cell membrane antigens associated with human T-cell leukemia virus in patients with AIDS. Science 220:859–862, 1983

  3. 3.

    Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Anler-Blin C, Vizinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L: Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871, 1983

  4. 4.

    Gelmann EP, Popovic M, Blayney D, Masw H, Sighu G, Stahl RE, Gallo RC: Proviral DNA of a retrovirus, human T-cell leukemia virus, in two patients with AIDS. Science 220:862–865, 1983

  5. 5.

    Montagnier I, Chermann JC, Barre-Sinoussi F: A new human T-lymphotropic retrovirus: Characterization and possible role in lymphadenopathy and acquired immune deficiency syndrome.In The Cancer Cell 3, Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1983 (in press).

  6. 6.

    Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M, Richardson E, Kalyanaraman VS, Mann D, Sidhu GD, Stahl RE, Zolla-Pazner S, Leibowitch J, Popovic M: Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 220:865–867, 1983

  7. 7.

    Sonnabend J, Witkin SS, Purtilo DT: Acquired immunodeficiency syndrome, opportunistic infections, and malignancies in male homosexuals. A hypothesis of etiologic factors in pathogenesis. JAMA 249:2370–2374, 1983

  8. 8.

    Witkin SS, Sonnabend J: Immune responses to spermatozoa in homosexual men. Fertil Steril 39:337–342, 1983

  9. 9.

    Hershe M, Reuben JM, Bogerd H, Rosenblum M, Bielski M, Mansell PWA, Rios A, Newell GR, Sonnenfeld G: Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production. Cancer Res 43:1365–1371, 1983

  10. 10.

    Reuben JM, Hersh EM, Mansell PW, Newell G, Rios A, Rossen R, Goldstein AL, McClure JE: Immunological characterization of homosexual males. Cancer Res 43:897–904, 1983

  11. 11.

    Goedert JJ, Neuland CY, Wallen WC, Greene MH, Mann DL, Murray C, Strong DM, Fraumeni JF Jr, Blattner WA: Amyl Nitrite May Alter T Lymphocytes in Homosexual Men. Lancet 1:412–415, 1982

  12. 12.

    Stahl RE, Friedman-Kien A, Dubin R, Marmor M, Zolla-Pazner S: Immunologic abnormalities in homosexual men. Relationship to kaposi's sarcoma. Am J Med 73:171–178, 1982

  13. 13.

    Rasmussen EO, Cooper KD, Kang K, White CR Jr. Regan DH, Hanifin JM: Immunosuppression in a homosexual man with Kaposi's sarcoma. J Am Acad Dermatol 6:870–879, 1982

  14. 14.

    Lew F, Tsang P, Solomon S, Selikoff IJ, Bekesi JG: Natural killer cell function and modulation by αIFN and IL2 in AIDS patients and prodromal subjects. J Clin Lab Immunol 14:115–121, 1984

  15. 15.

    Krown SE, Real FX, Cunningham-Rundles S, Myskowski P, Koziner B, Fein S, Mittelman A, Oettgen HF, Safai B: Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi's sarcoma. N Engl J Med 308:1071–1076, 1983

  16. 16.

    Rook AH, Masur H, Lane HC, Frederick W, Kasahara T, Macher AM, Djeu JY, Manischewitz JF, Jackson L, Fauci AS, Quinnan GV Jr: Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome. J Clin Invest 72:398–403, 1983

  17. 17.

    Herberman RB: Immunoregulation and natural killer cells. Mol Immunol 19:1313–1321, 1982

  18. 18.

    Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS: Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 309:453–458, 1983

  19. 19.

    Ikram H, Prince AM, Baker LN: Cytomegalovirus (CMV) antibody in male homosexuals: A source for CMV immune globulin. Vox Sang 44:173–177, 1983

  20. 20.

    Coutinho RA, Lelie N, Albrecht-Van-Lent P, Reerink-Brongers EE, Stootjesdijk L, Dees P, Nivard J, Huisman J, Reesink HW: Efficacy of a heat inactivated hepatitis B vaccine in male homosexuals: Outcome of a placebo controlled double blind trial. Br Med J (Clin Res) 286:1305–1308, 1983

  21. 21.

    Drew WL, Conant MA, Miner RC, Huang ES, Ziegler JL, Groundwater JR, Gullett JH, Volberding P, Abrams DI, Mintz L: Cytomegalovirus and Kaposi's sarcoma in young homosexual men. Lancet 2:125–127, 1982

  22. 22.

    Fawaz KA, Matloff DS: Viral hepatitis in homosexual men. Gastroenterology 81:537–538, 1981

  23. 23.

    Curran JW: AIDS-two years later. N Engl J Med 309:609–611, 1983

  24. 24.

    Ginsberg T, Glasky AJ: Inosiplex: An immuno-modulation model for the treatment of viral disease. Ann NY Acad Aci 284:128–138, 1977

  25. 25.

    Hadden JW, Lopez C, O'Reilly RJ, Hadden EM: Levamisole and inosiplex: Antiviral agents with immunopotentiating action. Ann NY Acad Sci 284:139–152, 1977

  26. 26.

    Rojo JM, Ogida G, Portoles MP: Enhancement and restoration of contact sensitivity reactions by isoprinosine. J Immunopharmacol 5:231–243, 1982

  27. 27.

    Portoles A, Ojida G, Rojo JM, Portoles MP, Barasovin I: Modulating effects of isoprinosine on lymphocyte proliferative response under immunodepression conditions. J Immunopharmacol 5:245–256, 1983

  28. 28.

    Balestrino C, Montesorro E, Nocera A, Ferrarini M, Hoffman T: Augmentation of human peripheral blood natural killer activity by methisoprinol. J Bio Resp Mod 2:577–585, 1983

  29. 29.

    Wybran J, Famaey JP, Gortz R, Dab I, Malfroot A, Appelboom T: Inosiplex (isoprinosine): A review of its immunological and clinical effects in disease. Adv Pharmacol Ther II 6:123, 1982

  30. 30.

    Renoux G, Renoux M, Guillaumin JM, Gouzien C: Differentiation and regulation of lymphocyte populations: Evidence for immunopotentiator-induced T cell recruitment. J Immunopharmacol 1:415–422, 1979

  31. 31.

    Renoux G, Renoux M, Guillaumin JM: Isoprinosine as an immunopotentiator. J Immunopharmacol 1:337–356, 1979

  32. 32.

    Wybran J, Govaerts A, Appelboom T: Inosiplex, a stimulating agent for normal human T-cells and human leucocytes. J Immunol 121:1184–1187, 1978

  33. 33.

    Wybran J: Immunomodulatory properties of isoprinosine in man: In vitro and in vivo data.In International Symposium on New Trends in Human Immunology and Cancer Immunotherapy, B Serrou, C Rosenfeld (eds). Paris, Doin, 1980, pp 1014–1020

  34. 34.

    Hadden JW, Hadden EM, Coffey RG: Isoprinosine augmentation of phytohemagglutinin-induced lymphocyte proliferation. Infect Immun 13:382–387, 1976

  35. 35.

    Tsang PH, Holland JF, Bekesi JG: Central role of T lymphocytes in specific recognition of tumor antigens in51Cr-leukocyte adherence inhibition. Cell Immunol 73:365–375, 1982

  36. 36.

    Reinherz EL, Kung PC, Goldstein G, Schlossman SF: Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci USA 76:4061–4065, 1979

  37. 37.

    Tsang KY, Pan JF, Gnagy MJ, Bristow CB, Fudenberg HH: Isoprinosine stimulation of interleukin-2 (IL-2) production by human lymphocyte. Fed Proc 42:446, 1983

  38. 38.

    Tsang KY, Fudenberg HH, Galbraith GMP: In vitro augmentation of interleukin-2 production and lymphocytes with the Tac antigen marker in patients with AIDS. N Engl J Med 310:987, 1984

  39. 39.

    Renoux G, Renoux M, Degenne D: Suppressor cell activity after isoprinosine treatment of lymphocytes from normal mice. Int J Immunopharmacol 1:239–241, 1979

  40. 40.

    Lanier LL, Engleman EG, Gatenby P, Babcock GF, Warner NL, Herzenberg LA: Correlation of functional properties of human lymphoid cell subsets and surface marker phenotypes using multi-parameter analysis and flow cytometry. Immunol Rev 74:143–160, 1983

  41. 41.

    Thomas Y, Rogozinski L, Irigoyen OH, Friedman SM, Kung PC, Goldstein G, Chess L: Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population. J Exp Med 154:459–467, 1981

  42. 42.

    Nicholson JKA, McDougal JS, Spira TJ, Cross GD, Jones BM, Reinherz EL: Immunoregulatory subsets of the T helper and T suppressor cell populations in homosexual men with chronic unexplained lymphadenopathy. J Clin Invest 73:191–201, 1984

Download references

Author information

Correspondence to J. George Bekesi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tsang, P.H., Tangnavarad, K., Solomon, S. et al. Modulation of T- and B-lymphocyte functions by isoprinosine in homosexual subjects with prodromata and in patients with acquired immune deficiency syndrome (AIDS). J Clin Immunol 4, 469–478 (1984).

Download citation

Key words

  • Isoprinosine
  • immune modulation
  • acquired immune deficiency syndrome
  • prodromal homosexuals