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 were examined using different schedules of the drug in mice infected with the Y strain. Parasitaemia at day 8 after infection among CsA-treated animals was usually higher than control infected non-treated mice. On the other hand, mortality analysis showed that animals CsA-treated either with 200 mg/kg 2 days before infection or with therapeutic doses (10 mg/kg every other day) showed almost the same mean time of death (35.8 and 38.2 days, respectively). 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 animals treated with a single dose of 200 mg/kg of CsA before or after infection 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 intense diffuse inflammatory reaction exhibiting mainly mononuclear cells in the heart. Immunofluorescence analysis by confocal microscopy revealed that macrophages are a major component of the inflammatory infiltrate in all groups of CsA-treated mice and also in the control group.
Calabrese
K S
KS
Laborat orio de Imunomodula-c-ao, Departamento de Protozoologia, Instituto Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, 21045-900, Rio de Janeiro, Brazil. calabres@gene.dbbm.fiocruz.br
Paradela
A S
AS
Zaverucha do Valle
T
T
Tedesco
R C
RC
Silva
S
S
Mortara
R A
RA
Gonçalves da Costa
S C
SC
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement; D014355:Chagas Disease / Q000188:drug therapy* / Q000401:mortality; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009205:Myocarditis / Q000188:drug therapy / Q000469:parasitology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D018512:Parasitemia / Q000188:drug therapy; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D013997:Time Factors; D014352:Trypanosomiasis / Q000188:drug therapy / Q000401:mortality
D007166:Immunosuppressive Agents; D016572:Cyclosporine