We examined the effects of recombinant rat inteferon‐gamma (IFN‐γ) injections on the parasitologic, serologic, immunologic and histopathologic features of acute and chronic experimental Trypanosoma cruzi (T. cruzi) infections in “l” rats. Upon infection at weaning, two rat groups were allocated to receive a 20‐day cycle of IFN‐γ injections, 20,000 IU/rat each, which started at 1, and 7 days post‐infection (pi). Treatment with IFN‐γ, initiated at either 1 or 7 days pi, resulted in comparatively lower peak parasitemias (P<0.02) but in similar levels of anti‐T. cruzi circulating antibodies and serum IFN‐γ activities. The latter appeared significantly increased during acute infection whereas biologically active tumor necrosis factor was virtually undetectable in serum from infected rats regardless of whether they had been given IFN‐γ or not. The prevalence of chronic focal myocarditis in IFN‐γ‐treated infected rats showed no differences with respect to the one recorded in control‐infected counterparts. The inverse CD4/CD8 ratio of spleen and lymph node T cells that usually accompanies chronic infection was reversed by IFN‐γ. Mononuclear cells carrying class III‐A and I‐E molecules, that were found to have increased at both compartments, appeared also modified upon IFN‐γ treatment with an overincrease of I‐A‐positive cells, and a normalization of I‐E‐bearing cells.

Se estudió la evolución de la artritis por adyuvante en ratas que habían sido infectadas previamente con Trypanosoma cruzi, con el objeto de evaluar su competencia inmunológica a través de la respuesta artrítica. La artritis por adyuvante se indujo en ratas adultas, endocriadas de ambos sexos, con 0.1 mi de adyuvante completo de Freund en la almohadilla plantar, en 2 lotes: a) inyectadas 90 días antes con 1 x 10(6) T. cruzi y b) testigos normales simultáneos. Se midieron, la lesión artrítica macroscópicamente con una escala semicuantitativa, y con microscopía óptica la histopatología de la lesión local y la del corazón, a los 180 días post-infecoión. La magnitud de las lesiones artríticas en las ratas con T. cruzi fue significativamente menor (p < 0.001) que la de los testigos, en todo el período. El infiltrado inflamatorio local, formado por linfocitos, plasmocitos y macrófagos fue significativamente menor (p < 0.001) en las ratas chagásicas, con respecto al de los testigos. Se postula que en las ratas que recibieron T. cruzi la respuesta artrítica menor podría deberse a una competición antigénica con los determinantes del parásito o a mecanismos inmunosupresores que interfieren en la producción de la entidad experimental.

The present study was undertaken in order to demonstrate that reinfection could modify parasitemia, serum antibodies, electrocardiographic patterns and/or myocardial lesions already observed in a rat model. Experimental groups IG: rats infected at weaning with 1 x 10(6) T. cruzi; RG: same as IG plus reinoculations each 30 days until completion on day 150; IG1: 51 day old infected rats; C: controls. A high parasitemia was detected in IG and RG until day 20 showing a tendency to become negative on day 30. No parasites were observed in RG after the first reinoculation which could not be attributed to the old age of the host since there was no parasitemia in IG1. Xenodiagnosis were negative in all three groups. Serum antibodies were not significantly modified in RG in comparison with IG, except for 7S antibodies, since RG showed higher titres in some days under study. No distinct patterns of basal ECG were observed in infected rats. The ajmaline test reduced the heart rate (HR) showing no treatment dependence. The PR, QaT and QRS were significantly lengthened in all groups regarding the basal one (p less than 0.05), except for the QaT in C. Besides, the PR and QaT alterations were greater in the infected rats (p less than 0.05). There was also present a wide variety of electric axis orientations, regarding the basal value, accompanied by morphological changes more evident in the RG. The incidence of cardiac lesions histologically detected in the infected group was significantly higher than in C (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Liver preneoplasia development in rats can be mimicked by an initiation-promotion model that induces the appearance of altered hepatocyte foci (FAH).Aims: We compare two initiation-promotion models to evaluate the presence of FAH or additional hepatic pathologies in which other organs were affected up to five month post treatment.Material and methods: FAH were induced in male adult Wistar rats with two doses of dietylnitrosamine (DEN, 150 mg/kg bw) followed by 4 doses per week (3 weeks) of 2-acetylaminofluorene (2-AAF, 20 mg/kg bw) or with one dose of DEN (200 mg/kg bw) followed by 2 doses per week (3 weeks) of 2-AAF. DEN 150, DEN 200 and control rats (received the vehicle of the drugs) groups were compared. Rats were euthanized immediately after the last dose of 2-AAF, at 3, 4 and 5 months (n = 3 for euthanasia times per group). Samples of livers, lungs, kidneys, pancreatic tissue and small bowel were processed for histological and immunohistochemical analysis.Results: FAH persisted for 5 months in all livers of the DEN groups. Three months after withdrawal of 2-AAF, one rat from DEN 150 group developed fibrosis and 5 months after 2-AAF removal another rat from the same group presented a microscopic hyperplastic nodule. Only the lungs had damages compatible with lesions induced by gavage-related reflux in DEN groups.Conclusion: We concluded that up to five month post treatments, FAH persisted in all the livers from DEN groups; livers from DEN 200 group showed no other hepatic lesions besides FAH, and only the lungs suffered pathological alterations in both treated groups.