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https://www.arca.fiocruz.br/handle/icict/51027
THE ANTI-TRYPANOSOMA CRUZI ACTIVITY OF POSACONAZOLE IN A MURINE MODEL OF ACUTE CHAGAS' DISEASE IS LESS DEPENDENT ON GAMMA INTERFERON THAN THAT OF BENZNIDAZOLE
Author
Affilliation
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Laboratório de Química Biológica, Centro de Biofísica y Bioquímica. Instituto Venezolano de Investigaciones Cientíicas. Apartado,Caracas, Venezuela
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Laboratório de Química Biológica, Centro de Biofísica y Bioquímica. Instituto Venezolano de Investigaciones Cientíicas. Apartado,Caracas, Venezuela
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil
Abstract
We have investigated the influences of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) on the efficacy of posaconazole (POS) treatment of acute experimental infections with Trypanosoma cruzi; the standard drug, benznidazole (BZ), was used as a positive control. Wild-type (WT) mice infected with T. cruzi and treated with POS or BZ had no parasitemia, 100% survival, and cure rates of 86 to 89%. IFN-gamma-knockout (KO) mice infected with T. cruzi and treated with BZ controlled the infection during treatment but relapsed after the drug pressure ceased and had 0% survival, while those receiving POS better controlled the infection after the end of treatment and had 70% survival (P < 0.0001 compared to the results for both untreated and BZ-treated animals). IL-12-KO mice infected and treated with POS or BZ had intermediate results, displaying enhanced parasitemia, decreased survival (77 to 83%), and reduced cure rates (35 to 39%) compared with those of the WT animals. Our results demonstrate that either IFN-gamma or IL-12 deficiency reduces the efficacy of POS or BZ in this experimental model but also indicate that the anti-T. cruzi activity of POS is much less dependent on the activity of IFN-gamma than that of BZ is
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