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

Because benznidazole (BZL) was found to downregulate nitric oxide (NO) and cytokine synthesis by murine macrophages, we analyzed the potential immunol ogical repercussions of BZL treatment in Trypanosoma cruzi-infected rats. T o evaluate whether the effects of BZL were also observed in the presence of an immunostimulating cytokine, four groups of acutely infected rats were s ubjected to one of the following 20-day therapeutic schedules: (1) a curati ve BZL oral regimen, (2) recombinant interferon (IFN-gamma) injections, (3) a suboptimal BZL regimen (25 % of curative dose), (4) the latter plus IFN- gamma. All BZL doses markedly reduced NO-derived metabolites either in the circulation or in cultured macrophage supernatants. This was observed in ra ts simultaneously treated with IFN-gamma, which contrasted with the augment ed NO production seen in animals given this cytokine alone. The untreated r ats, and groups receiving monotherapy with IFN-gamma or 25% BZL, had increa sed circulating interleukin (IL)-1 beta and IL-2 levels, which were reduced in those given BZL plus IFN-gamma. Although combined treatment failed to c ause the virtually undetectable blood parasite levels induced by optimal BZ L doses, chronic myocardial lesions were reduced to the same extent as in t hose receiving the curative schedule. The beneficial effects of BZL in this trypanosomiasis may also depend on some immunomodulating influences.