Study of acute chagasic mice under immunosuppressive therapy by cyclosporin A: modulation and confocal analysis of inflammatory reaction

The in vivo effects of cyclosporin A (CsA) on Trypanosoma cruzi infection w ere examined using different schedules of the drug in mice infected with th e Y strain. Parasitaemia at day 8 after infection among CsA-treated animals was usually higher than control infected non-treated mice. On the other ha nd, mortality analysis showed that animals CsA-treated either with 200 mg/k g 2 days before infection or with therapeutic doses (10 mg/kg every other d ay) showed almost the same mean time of death (35.8 and 38.2 days, respecti vely). In these groups mice died 50% less than control infected non-treated ones. The mean time of death in the animals treated with 200 mg/kg 5 days after infection and in infected non-treated control mice were respectively 29.0 and 22.6 days. The kinetics analysis of the leukocyte population of an imals treated with a single dose of 200 mg/kg of CsA before or after infect ion did not show the alternate pattern of leukopenia/leukocytosis observed in control groups of infected mice but differential cell counts indicated a modulatory action upon circulating leukocytes of therapeutic doses of CsA. The animals treated with any of the CsA schedules showed a moderate to int ense diffuse inflammatory reaction exhibiting mainly mononuclear cells in t he heart. Immunofluorescence analysis by confocal microscopy revealed that macrophages are a major component of the inflammatory infiltrate in all gro ups of CsA-treated mice and also in the control group. (C) 2000 Elsevier Sc ience B.V. All rights reserved.