Role of cytokines and lymphocytes on the efficacy of

Posaconazole and Benznidazole in treatment of

experimental acute Trypanosoma cruzi infection

Alvaro José Romanha

Centro de Pesquisa René Rachou – FIOCRUZ - MG

Rio de Janeiro, July 2009.

WT

IFN- KO

IL-12 KO

WT

IFN- KO

IL-12 KO

Mortality, survival and cure of WT, IFN-γ-KO and IL-12-KO mice infected with T.cruzi Y strain and treated with posaconazole and benznidazole

Treatment

Mortality, survival and cure of WT, IFN-γ-KO and IL-12-KO mice infected with T.cruzi Y strain and treated with posaconazole and benznidazole

Mortality, survival and cure of WT, IFN-γ-KO and IL-12-KO mice infected with T.cruzi Y strain and treated with posaconazole and benznidazole

Conclusion:

Our results demonstrate that either IFN-γ or IL-12 deficiency reduces

the efficacy of POS or BZ in the acute murine infection with T.cruzi but

also indicate that the anti-T.cruzi activity of POS is much less

dependent on the activity of IFN-γ than that of BZ.

WT

LTCD4+ KO

LTCD8+ KO

LB KO

WT

LTCD4+ KO

LTCD8+ KO

LB KO

Survival and cure of WT and CD4+ T-lymphocyte, CD8+ T-lymphocyte, and B-lymphocyte-KO mice infected with the Y strain of T.cruzi and treated with POS or BZ

Conclusion:

The absence of different lymphocytes’ activities has distinct effects

on the efficacy of POS and BZ in the acute murine infection with

T.cruzi, probably reflecting different parasite stages preferentially

targeted by the two drugs and distinct cooperation patterns with the

host immune system.

Collaborators:

Marcela L. Ferraz e Rosana O. AlvesLaboratório de Parasitologia Celular e Molecular, Centro de Pesquisa René Rachou,

FIOCRUZ-MG;

Ricardo T. GazzinelliLaboratório de Imunopatologia, Centro de Pesquisa René Rachou, FIOCRUZ-MG e

Departamento de Bioquímica e Imunologia, ICB-UFMG;

Julio A. UrbinaLaboratório de Química Biológica, Centro de Biofísica y Bioquímica, Instituto Venezolano de

Investigaciones Científicas, Venezuela