Benznidazole is recommended in Brazil for the treatment of Trypanosoma cruzi infection in acute and early chronic phases of Chagas' disease. Observations by others have indicated a higher incidence of neoplasias in immunosuppressed patients, presenting Chagas' disease reactivation, submitted to treatment with benznidazole. In the present study, we investigated whether there is a potentiation in the generation of lymphomas in chronically infected mice, treated with immunosuppressive drugs and benznidazole. For this, 142 Swiss mice chronically infected with the 21 SF strain of T. cruzi and 72 normal Swiss mice were used. Both infected and normal mice were divided into experimental groups and submitted to one of the following treatment regimens: benznidazole alone; immunosuppressive drugs (azathioprine, betamethasone and cyclosporin); a combination of immunosuppressive drugs and benznidazole; and untreated controls. In the infected group treated with benznidazole, one mouse developed a non-Hodgkin's lymphoma. This finding has been interpreted as a spontaneous tumor of mice. The study of the chronically infected mice treated with the combination of immunosuppressive drugs and benznidazole demonstrated an absence of lymphomas or other neoplasias. These findings support the indication of benznidazole, as the drug of choice, for immunosuppressed patients that develop a reactivation of Chagas' disease.
Acute infection with Trypanosoma cruzi results in intense
myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The
evolution toward this chronic cardiac form occurs in approximately 30% of all
cases of T. cruzi infection. Suppression of delayed type
hypersensitivity (DTH) has been proposed as a potential explanation of the
indeterminate form. We investigated the effect of cyclophosphamide (CYCL)
treatment on the regulatory mechanism of DTH and the participation of heart
interstitial dendritic cells (IDCs) in this process using BALB/c mice
chronically infected with T. cruzi. One group was treated with
CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by
intradermal injection of T. cruzi antigen (3 mg/mL) in the
hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin
test revealed increased thickness in antigen-injected footpads, which was more
evident in the mice treated with CYCL than in those mice that did not receive
treatment. The thickened regions were characterised by perivascular infiltrates
and areas of necrosis. Intense lesions of the myocardium were present in
three/16 cases and included large areas of necrosis. Morphometric evaluation of
lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled
with specific antibodies (CD11b and CD11c) and T. cruzi
antigens were detected using a specific anti-T. cruzi antibody.
Identification of T. cruzi antigens, sequestered in these cells
using specific anti-T. cruzi antibodies was done, showing a
significant increase in the number of these cells in treated mice. These results
indicate that IDCs participate in the regulatory mechanisms of DTH response to
T. cruzi infection.
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