, Volume 84, Issue 2–3, pp 171–180 | Cite as

Effect of levamisole on experimental paracoccidioidomycosis in the Syrian hamster: Immunologic and histopathologic correlation

  • M. T. Rezkallah-Iwasso
  • N. G. S. Mota
  • M. C. G. Gomes
  • M. R. Montenegro


The effect of levamisole (LMS) was studied in hamsters inoculated with live yeast phase culture of Paracoccidioides brasiliensis by intratesticular route. One group started LMS therapy at an early stage of infection (LMS3 group), when the animals were immunocompetent, and another group was treated in a later stage, when the immune response was already depressed (LMS12 group). As control, one group was not treated.

The alterations induced by levamisole were studied by immunologic and histopathologic parameters. Compared to controls, the LMS3 group presented normal levels of cellular immune response and inflammatory reaction characterized by compact epithelioid granuloma during a longer period of time. In addition, this group showed a lower incidence of amyloidosis and lower fungi proliferation in the lesions. In the LMS12 group a transient enhancement was noteworthy of cellular immune response with maintenance of the compact pattern of the epithelioid granuloma as in the LMS3 group; however, the number of fungi and incidence of amyloidosis were similar to controls. The differences between both treated groups may be accounted for by some factors such as host immune competence, timing and total dose of LMS administered. Levamisole may be of value as additional therapy in paracoccidioidomycosis.


Amyloidosis Cellular Immune Response Levamisole Syrian Hamster Phase Culture 
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.
    Al-Ibrahim, M. S., Holzman, R. S. & Lawrence, S., 1977. Concentrations of levamisole required for enhanced proliferation of human lymphocytes and phagocytosis by macrophages. J. Infect.Dis. 135: 517–523.Google Scholar
  2. 2.
    Bast, R. C., Zbar, B., Borsos, T. & Rapp, H. J., 1974. BCG and Cancer. New Engl. J. Med. 290: 1413–1420.Google Scholar
  3. 3.
    Berd, D., 1978. Effects of Corynebacterium parvum on immunity. Pharmac. Ther. A 2: 373–395.Google Scholar
  4. 4.
    Bice, D.E., Lopez, M., Rothschild, H. & Salvaggio, J., 1974. Comparison of Candida-delayed hypersensitivity skin test size with lymphocyte transformation, migration inhibitory factor production and antibody titer. Int. Arch. Allergy 47: 54–62.Google Scholar
  5. 5.
    Chensue, S. W., Boros, D. L. & David, C. S., 1980. Regulation of granulomatous inflammation in murine schistosomiasis. In vitro characterization of T lymphocyte subsets involved in the production and suppression of MIF. J. Exp. Med. 151: 1398–1412.Google Scholar
  6. 6.
    Cunningham, F. M., Ford-Hutchinson, A. W., Oliver, A. M., Smith, M. J. H. & Walker, J. R., 1978. The effects of D-penicillamine and levamisole on leucocyte chemotaxis in the rat. Br. J. Pharmac. Chemother. 63: 119–123.Google Scholar
  7. 7.
    Daddi, G., De Ritis, G., Mancini, P. A. & Stefanini, A., 1979. May levamisole be helpful in aspergillosis? Boll. Ist. Sieroter, Milan. 58: 273–275.Google Scholar
  8. 8.
    Delespesse, G., Vrijens, R., Maubeuge, J., Hudson, D., Kennes, B. & Govaerts, A., 1977. Influence of levamisole on the immune response of old people. Int. Archs. Allergy Appl.Immunol. 54: 151–157.Google Scholar
  9. 9.
    Druet, R. L. & Janigan, D. T., 1966. Experimental amyloidosis. Rates of induction, lymphocyte depletion and thymic atrophy. Am. J. Pathol. 49: 911–923.Google Scholar
  10. 10.
    Fava Netto, C., 1972. The serology of paracoccidioidomycosis: present and future trends. In: Pan American Symposium on Paracoccidioidomycosis, I, Medellin, 1971. Proceedings. Washington, PAHO. Scient Publ. No. 254, pp. 209–213.Google Scholar
  11. 11.
    Fava Netto, C., Vegas, V. S., Sciannamea, I. M. & Guarnieri, D. B., 1969. Antígeno polissacarídico do Paracoccidioides brasiliensis. Estudo do tempo de cultivo do P. brasiliensis necessário ao preparo do antígeno. Rev. Inst. Med. Trop. S. Paulo 11: 177–181.Google Scholar
  12. 12.
    Fischer, G. W., Podgore, J. K., Bass, J. W., Kelley, J. L. & Kobayashi, G. Y., 1975. Enhanced host defense mechanisms with levamisole in suckling rats. J. Infect. Dis. 132: 578–581.Google Scholar
  13. 13.
    Golding, H., Golding, B., Jacobson, R., Lomnitzer, R., Koornhof, H. I. & Rabson, A. R., 1976. In vitro reversal of cellular unresponsiveness induced by levamisole. Clin. Exp. Immunol. 26: 295–301.Google Scholar
  14. 14.
    Hadden, J. W., Coffey, G., Hadden, E. M., Lopez-Corrales, E. & Sunshine, G. H., 1975. Effects of levamisole and imidazole on lymphocyte proliferation and cyclic nucleotide levels. Cell. Immunol. 20: 98–103.Google Scholar
  15. 15.
    Hoebeke, J. & Franchi, G., 1973. Influence of tetramisole and its optical isomers on the mononuclear phagocytic system. J. Reticuloendothel. Soc. 14: 317–323.Google Scholar
  16. 16.
    Hofmann, E., Sauter, C. H. R. & Reinhardt, E., 1979. Zellulare Immunität: Leukoziten-Migrationsinhibition in vitro korreliert nicht mit dem Tuberkulin-Hauttest. Schweiz. Med. Wochenschr. 109: 1376–1378.Google Scholar
  17. 17.
    Iabuki, K. & Montenegro, M. R., 1979. Experimental paracoccidioidomycosis in the Syrian hamster: Morphology, ultrastructure and correlation of lesions with presence of specific antigens and serum levels of antibodies. Mycopathologia 67: 131–141.Google Scholar
  18. 18.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265–275.Google Scholar
  19. 19.
    Michalevicz, R., Many, A., Ramot, B. & Trainin, N., 1978. The in vitro effect of thymic humoral factor and levamisole on peripheral blood lymphocytes in systemic lupus erythematosus patients. Clin. Exp. Immunol. 31: 111–115.Google Scholar
  20. 20.
    Musatti, C. C., Rezkallah, M. T., Mendes, E. & Mendes, N. F., 1976. In vivo and in vitro evaluation of cell-mediated immunity in patients with paracoccidioidomycosis. Cell. Immunol. 24: 365–378.Google Scholar
  21. 21.
    O'Reilly, R. J., Chibbaro, A., Wilmot, R., Lopez, C., 1977. Correlation of clinical and virus specific immune response following levamisole therapy of recurrent herpes progenitalis. Ann. N.Y. Acad. Sci. 284: 161–170.Google Scholar
  22. 22.
    Ouchterlony, O., 1949. Antigen-antibody reaction in gels. Acta Pathol. Microbiol. Scand. 26: 507–515.Google Scholar
  23. 23.
    Pelley, R. P. & Warren, K. S., 1978. Immunoregulation in chronic infectious disease: schistosomiasis as a model. J. Invest. Dermatol. 71: 49–55.Google Scholar
  24. 24.
    Peraçoli, M. T. S., Mota, N. G. S. & Montenegro, M. R., 1982. Experimental paracoccidioidomycosis in the Syrian hamster. Morphology and correlation of lesions with humoral and cell-mediated immunity. Mycopathologia 79: 7–17.Google Scholar
  25. 25.
    Primack, W. A., 1978. Cimetidine and renal-allograft rejection. Lancet 1: 824–825.Google Scholar
  26. 26.
    Ramot, B., Biniaminov, M., Shoham, C. H., Rosenthal, E., 1976. Effect of levamisole on E-rosette-forming cells in vivo and in vitro in Hodgkin's disease. New Engl. J. Med. 294: 809–811.Google Scholar
  27. 27.
    Renoux, G., 1980. L'immunopharmacologie au service de l'immunothérapie. Nouv. Presse Med. 9: 1633–1636.Google Scholar
  28. 28.
    Renoux, G. & Renoux, M., 1972. Antigenic competition and nonspecific immunity after a rickettsial infection in mice: restoration of antibacterial immunity by phenyl-imidothiazole treatment. J. Immunol. 109: 761–765.Google Scholar
  29. 29.
    Renoux, G. & Renoux, M., 1977. Méchanisms d'action du levamisole, stimulant des réponses d'immunité cellulaire. Ann. Immunol. 228C: 275–277. zole treatment. J. Immunol. 109: 761–765.Google Scholar
  30. 30.
    Renoux, G., Renoux, M., Teller, M. N., McMahon, S. & Guillaumin, J. M., 1976. Potentiation of T-cell mediated immunity by levamisole. Clin. Exp. Immunol. 25: 288–296.Google Scholar
  31. 31.
    Restrepo, A., Greer, D. L. & Vasconcellos, M., 1973. Paracoccidioidomycosis, a review. Review Med. Vet. Mycol. 8: 97–123.Google Scholar
  32. 32.
    Restrepo, A. M., Restrepo, M., Restrepo, F., Aristizábal, L., Moncada, L. H. & Vélez, H., 1978. Immune responses in paracoccidioidomycosis. A controlled study of 16 patients before and after treatment. Sabouraudia 16: 151–163.Google Scholar
  33. 33.
    Ridley, M. J., Marianayagam, Y. & Spector, W. G., 1982. Experimental granulomas induced by mycobacterial immune complexes in rats. J. Pathol. 136: 59–72.Google Scholar
  34. 34.
    Robledo, M. A., Graybill, J. R., Ahrens, J., Restrepo, A., Drutz, D. J. & Robledo, M., 1982. Host defense against experimental paracoccidioidomycosis. Am. Rev. Respir. Dis. 125: 563–567.Google Scholar
  35. 35.
    Rosenthal, C. J. & Franklin, E. C., 1977. Amyloidosis and amyloid proteins. Recent Adv. Clin. Immunol. (1): 41–76.Google Scholar
  36. 36.
    Sampson, D. & Lui, A., 1976. The effect of levamisole on cell-mediated immunity and suppressor cell function. Cancer Res. 36: 952–955.Google Scholar
  37. 37.
    Scheinberg, M. A. & Cathcart, E. S., 1974. Casein induced experimental amyloidosis. III. Response to mitogens, allogenic cells and graft versus host reaction in the murine model. Immunology 27: 953–963.Google Scholar
  38. 38.
    Scheinberg, M. A., Goldstein, A. L. & Cathcart, E. S., 1976. Thymosin restores T cell function and reduces the incidence of amyloid disease in casein-treated mice. J. Immunol. 116: 156–158.Google Scholar
  39. 39.
    Schmidt, M. E. & Douglas, S. D., 1976. Effects of levamisole of human monocyte function and immunoprotein receptors. Clin. Immunol. Immunopathol. 6: 299–305.Google Scholar
  40. 40.
    Spector, W. G., Marianayagam, Y. & Ridley, M. J., 1982. The role of antibody in primary and reinfection BCG granulomas of rat skin. J. Pathol. 131: 41–57.Google Scholar
  41. 41.
    Symoens, J.& Rosenthal, M., 1977. Levamisole in the modulation of the immune response: the current experimental and clinical state. J. Reticuloendothel. Soc. 21: 175–221.Google Scholar
  42. 42.
    Szpilman, H., Luft, S., Glínska-Urban, D., Fischer, W. & Plachecka, M., 1976. Levamisole and cell-mediated immunity and serum immunoglobulins in rheumatoid arthritis. Lancet 2: 208–209.Google Scholar
  43. 43.
    Tripodi, D., Parks, L. C. & Brugmans, J., 1973. Drug-in-duced restoration of cutaneous delayed hypersensitivity in anergic patients with cancer. New Engl. J. Med. 289: 354–357.Google Scholar
  44. 44.
    Unanue, E. R., 1978. The immune granulomas. In: Immunological Diseases, Talmage, D. W., Rose, B., Austen, K. F. & Vaugham, J. W., (eds.). Vol. I, pp. 297–306, Little Browns, U.S.A.Google Scholar
  45. 45.
    Verhaegen, H., Verbruggen, F., Verhaegen-Declerg, M. L. & De Cree, J., 1974. Effects du levamisole sur les réactions cutanées d'hypersensibilité retardée. Nouv. Presse Méd. 2: 2483–2485.Google Scholar
  46. 46.
    Visco, G., Demartino, G., Guarascio, P., Severini, F., Carvelli, C., Narciso, P., Sette, P., Tossini, G. & Amini, M., 1980. L'immunoterapia attiva aspecifica. G. Mal. Infett. Parassit. 32: 508–551.Google Scholar
  47. 47.
    Warren, K. S., Domingo, E. O. & Cowan, R. B. T., 1967. Granuloma formation arround schistosome eggs as a manifestation of delayed hypersensitivity. Am. J. Pathol. 51: 735–756.Google Scholar
  48. 48.
    Whitcomb, M. E., Merluzzi, V. J. & Cooperband, S. R., 1976. The effect of levamisole on human lymphocyte mediator production in vitro. Cell. Immunol. 21: 272–277.Google Scholar
  49. 49.
    Wright, D. G., Kirkpatrick, C. H. & Gallin, J. I., 1977. Effects of levamisole on normal and abnormal leucocyte locomotion. J. Clin. Invest. 59: 941–950.Google Scholar
  50. 50.
    Zeiss, C. Oberkochen, 1969. Integrating and grain-size disks for turret eyepiece and projection screens. Oberkochen, 37 pp.Google Scholar

Copyright information

© Dr W. Junk Publishers 1984

Authors and Affiliations

  • M. T. Rezkallah-Iwasso
    • 1
  • N. G. S. Mota
    • 1
  • M. C. G. Gomes
    • 2
  • M. R. Montenegro
    • 3
  1. 1.Department of Microbiology and ImmunologyUNESPBotucatu, São PauloBrazil
  2. 2.Department of StatisticsUNESPBotucatu, São PauloBrazil
  3. 3.Department of PathologyUNESPBotucatu, São PauloBrazil

Personalised recommendations