Treatment with benznidazole and its immunomodulating effects on experimentally Trypanosoma cruzi-infected rats

PIAGGIO E; ROGGERO E; PITASHNY M; WIETZERBIN J; BOTTASSO O; REVELLI S; BOTTASSO OSCAR

PARASITOLOGY RESEARCH

SPRINGER

Lugar: Alemania; Año: 2001 vol. 87 p. 539 - 547

0932-0113

To get someinsight into this question we took advantage of an experimental model developedin our laboratory, in which infection with T.cruzi in inbred strain ?l? rats reproduces several aspects of the clinicopathological features ofhuman chagasic infection. In fact, upon the experimental inoculation atweaning, the disease shows an acute phase that self-resolves by day 30postinfection (pi) leaving place to a chronic infection wherein 60-80 % ofthese rats develop a mild focal myocarditis. In addressing this issue, thequestion arises, however, to what extend eventual immunological changes can beattributed to a direct effect of BZL or to a decreased severity of the acutedisease resulting from its anti-parasitic activity. Blocking in vivoeffects of BZL, if present, could manifest by also applying an immunointerventionof recognized up-regulating effects on the synthesis of NO and other cytokinesplaying a role in the immune response against intracellular pathogens. Topursue this, a group of rats were also given IFN-γ since this cytokine is knownto exert a broad range of stimulating activities on the production of severalcytokines, as well as relevant biologic response modifiers, like theIFN-γ-transcriptionally induced iNOS-dependent NO synthesis in macrophages. Given thisbackground, a study was conducted by which experimentally T.cruzi-infectedrats subjected to BZL and/or IFN-γ treatment were investigated for thefollowing parameters(1) the systemic repercussion of the acute disease,in terms of parasitemias and serum levels of nitrite-nitrate, TNF-α, IL-1β andIL-2, (2) in vitro replication of T.cruzi in peritonealmacrophages and the subsequent production of nitrite-nitrate, TNF-α and IL-1β,(3) the characteristics of myocardial lesions developed during the chronicphase.