Effects of levamisole on experimental infections by Plasmodium berghei in mice

Melendez C., Enrique; Krettli, Antoniana U.

doi:10.1590/S0037-86821987000400002

Abstracts

Levamisole (phenylimidothiazol), considered a strong immunostimulant, when administered to healthy Swiss mice did not cause a significant increase in -the weight of their thymus, liver and spleen, even though the drug was used at different times before removing such organs. High doses ofdrug used in the 4-day prophylactic scheme had no antimalarial effect. However, when given to malaria infected mice 24 hours before, at the same time, and 24 hours after the inoculation of a chloroquine-sensitive or a chloroquine-resistant strain of Plasmodium berghei small doses of the drug induced a somewhat decreased parasitemia, the dose of 1 mg/kg body weight before the inoculum being the best scheme. The mortality rates by malaria in the levamisole treated groups were also delayed although all mice finally died. The data suggest that levamisole may display a stimulant effect on the depressed immune response caused by malaria.

Malaria; Plasmodium berghei; Chloroquine-resistant strain; Levamisole; Immunostimulation

Levamisol (fenilimidotiazol), considerado urn potente imunoestimulante, quando administrado a camundongos suíços não causou aumento significante nos pesos do timo, figado ou baço, apesar de a droga ter sido usada em diferentes tempos antes da remoção desses órgãos. Doses elevadas da droga usadas no esquema profilático de 4 dias não tiveram efeito antimalárico. Entretanto quando dada a camundongos com malária, 24 horas antes, ao mesmo tempo ou 24 horas após inoculação de uma cepa de Plasmodium berghei cloroquina-sensível ou uma cepa cloroquina- resistente o levamisol reduziu, ainda que discretamente, a parasitemia nos grupos tratados, sendo a dose de 1 mg/kg o melhor esquema. Foi observado também atraso na mortalidade por malária nos grupos tratados com o levamisol. No entanto, todos os animais morreram. Os dados sugerem que o levamisol tem efeito imunoestimulante, ainda que discreto, na resposta imune de animais, deprimida pela malária.

Malária; Plasmodium berghei; Cepa cloroquina-resistente; Levamisol; Imunoestimulante

ARTICLES

Effects of levamisole on experimental infections by Plasmodium berghei in mice

Enrique Melendez C.^I; Antoniana U. Krettli^II

^ISección de Parasitología, Escuela de Medicina, Univerdad Centro Occidental "Lisandro Alvarado", Apartado 400, Barquisimeto, Venezuela

^IIDepartamento de Parasitología, ICB, Universidade Federal de Minas Gerais and Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brasil

^{Adress to correspondence} Adress to correspondence: A.U. Krettli. Av. Augusto de Lima 1715. 30 190 Belo Horizonte, MG, Brazil.

ABSTRACT

Levamisole (phenylimidothiazol), considered a strong immunostimulant, when administered to healthy Swiss mice did not cause a significant increase in -the weight of their thymus, liver and spleen, even though the drug was used at different times before removing such organs. High doses ofdrug used in the 4-day prophylactic scheme had no antimalarial effect. However, when given to malaria infected mice 24 hours before, at the same time, and 24 hours after the inoculation of a chloroquine-sensitive or a chloroquine-resistant strain of Plasmodium berghei small doses of the drug induced a somewhat decreased parasitemia, the dose of 1 mg/kg body weight before the inoculum being the best scheme. The mortality rates by malaria in the levamisole treated groups were also delayed although all mice finally died. The data suggest that levamisole may display a stimulant effect on the depressed immune response caused by malaria.

Keywords: Malaria. Plasmodium berghei. Chloroquine-resistant strain. Levamisole. Immunostimulation.

RESUMO

Levamisol (fenilimidotiazol), considerado urn potente imunoestimulante, quando administrado a camundongos suíços não causou aumento significante nos pesos do timo, figado ou baço, apesar de a droga ter sido usada em diferentes tempos antes da remoção desses órgãos. Doses elevadas da droga usadas no esquema profilático de 4 dias não tiveram efeito antimalárico. Entretanto quando dada a camundongos com malária, 24 horas antes, ao mesmo tempo ou 24 horas após inoculação de uma cepa de Plasmodium berghei cloroquina-sensível ou uma cepa cloroquina- resistente o levamisol reduziu, ainda que discretamente, a parasitemia nos grupos tratados, sendo a dose de 1 mg/kg o melhor esquema. Foi observado também atraso na mortalidade por malária nos grupos tratados com o levamisol. No entanto, todos os animais morreram. Os dados sugerem que o levamisol tem efeito imunoestimulante, ainda que discreto, na resposta imune de animais, deprimida pela malária.

Palavras-chave: Malária. Plasmodium berghei. Cepa cloroquina-resistente. Levamisol. Imunoestimulante.

Full text available only in PDF format.

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Recebido para publicação em 3/11/86.

Part of this work was presented at the Congress of Parasitology, Equador, 1985. Work supported by CNPq- Brazil.

1. Bygbjer IC, Jepsen S, Theander TG. Lymphocyte response to purified Plasmodium falciparum antigens during and after malaria. Acta Tropica 43: 55-62, 1986.
2. Finerty JF, Krehl EP. Cyclophosphamide pretreatment and protection against malaria. Infection and Immunity 14: 1103-1105, 1976.
3. Greenwood BM, Odulaju AJ, Straton D. Lymphocyte changes in acute malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 71:408-410, 1977.
4. Hoebeke J, Franchi G. Influence of tetramisole and its optical isomers on the mononuclear phagocytic system. Journal of Reticuloendothelial Society 14: 317-323, 1973.
5. Krettli AU, Brener Z. Therapeutic activity of some sulfonamide compounds on normal and chloroquine-resistant strains of Plasmodium berghei Revista do Instituto de Medicina Tropical de São Paulo 10: 389-393, 1968.
6. Krettli AU, Lima-Pereira FE. Immunosuppression in protozoal infections. In: Levandowsky M, Hunter SH (eds.) Biochemistry and Physiology of Protozoa 4: 431- 458, Academic Press, New York, 1981.
7. Krettli AU, Nussenzweig RS. Depletion of T and B lymphocytes during malarial infections. Cellular Immunology 13: 440-446, 1974.
8. Oliveira-Lima A, Javierre MQ, Silva WD, Câmara DS. Immunological phagocytosis: effect of drugs on phos-phodiesterase activity. Experientia 30: 945-946, 1974.
9. Poels LG, Nieckerk CC. Plasmodium berghei: Immunosuppresion and hyperimmunoglobulinemia. Experimental Parasitology 42: 235-247, 1977.
10. Symoens J, Rosenthal M. Levamisole in the modulation of the immune response: the current experimental and clinical state. Journal of Reticuloendothelial Society 21: 175-221, 1977.
11. Targett GAT. Chemotherapy and the immune response in parasitic infections. Parasitology 90: 661-673,1985.
12. Tosta CE, Nicolau F. Possível efeito do levamisole na malária: aumento específico e inespecifico da fagocitose. Ciência e Cultura 28: 612, 1976.
13. Wyler DJ. Peripheral lymphocyte subpopulations in human falciparum malaria. Clinical and Experimental Immunology 23: 471-476, 1976.
14. Yoeli M. Studies on P. berghei in nature and under experimental conditions. Transactions of the Royal Society of Tropical Medicine and Hygiene 59:255-276,1965.

Adress to correspondence:

A.U. Krettli. Av. Augusto de Lima 1715.

30 190

Belo Horizonte, MG, Brazil.

Publication Dates

Publication in this collection
29 May 2013
Date of issue
Dec 1987

History

Accepted
03 Nov 1986
Received
03 Nov 1986

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Bygbjer IC, Jepsen S, Theander TG. Lymphocyte response to purified Plasmodium falciparum antigens during and after malaria. Acta Tropica 43: 55-62, 1986.

[2] 2. Finerty JF, Krehl EP. Cyclophosphamide pretreatment and protection against malaria. Infection and Immunity 14: 1103-1105, 1976.

[3] 3. Greenwood BM, Odulaju AJ, Straton D. Lymphocyte changes in acute malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 71:408-410, 1977.

[4] 4. Hoebeke J, Franchi G. Influence of tetramisole and its optical isomers on the mononuclear phagocytic system. Journal of Reticuloendothelial Society 14: 317-323, 1973.

[5] 5. Krettli AU, Brener Z. Therapeutic activity of some sulfonamide compounds on normal and chloroquine-resistant strains of Plasmodium berghei Revista do Instituto de Medicina Tropical de São Paulo 10: 389-393, 1968.

[6] 6. Krettli AU, Lima-Pereira FE. Immunosuppression in protozoal infections. In: Levandowsky M, Hunter SH (eds.) Biochemistry and Physiology of Protozoa 4: 431- 458, Academic Press, New York, 1981.

[7] 7. Krettli AU, Nussenzweig RS. Depletion of T and B lymphocytes during malarial infections. Cellular Immunology 13: 440-446, 1974.

[8] 8. Oliveira-Lima A, Javierre MQ, Silva WD, Câmara DS. Immunological phagocytosis: effect of drugs on phos-phodiesterase activity. Experientia 30: 945-946, 1974.

[9] 9. Poels LG, Nieckerk CC. Plasmodium berghei: Immunosuppresion and hyperimmunoglobulinemia. Experimental Parasitology 42: 235-247, 1977.

[10] 10. Symoens J, Rosenthal M. Levamisole in the modulation of the immune response: the current experimental and clinical state. Journal of Reticuloendothelial Society 21: 175-221, 1977.

[11] 11. Targett GAT. Chemotherapy and the immune response in parasitic infections. Parasitology 90: 661-673,1985.

[12] 12. Tosta CE, Nicolau F. Possível efeito do levamisole na malária: aumento específico e inespecifico da fagocitose. Ciência e Cultura 28: 612, 1976.

[13] 13. Wyler DJ. Peripheral lymphocyte subpopulations in human falciparum malaria. Clinical and Experimental Immunology 23: 471-476, 1976.

[14] 14. Yoeli M. Studies on P. berghei in nature and under experimental conditions. Transactions of the Royal Society of Tropical Medicine and Hygiene 59:255-276,1965.