Cyclophosphamide-induced immunosuppression protects cardiac noradrenergic nerve terminals from damage by Trypanosoma cruzi infection in adult rats.
Trypanosoma cruzi-infected juvenile rats develop severe cardiac sympathetic denervation in parallel with acute myocarditis. This aspect has not been studied in adult rats, thought to be resistant to this infection. The mechanism involved in T. cruzi-induced neuronal damage remains to be completely elucidated. In juvenile rats, the mortality during the acute phase depends on T. cruzi populations, ranging from 30% to 100%. Therefore, studies of mechanisms through hazardous procedures such as immunosuppression are restricted. The current paper shows that adult rats infected with T. cruzi (Y strain) develop severe acute myocarditis and cardiac sympathetic denervation, despite null mortality and virtual absence of patent parasitaemia followed by negative haemoculture. Recovery from the myocarditis and denervation occurred but PCR studies showed persistence of parasite DNA at least until day 111 post inoculation. Immunosuppression by cyclophosphamide treatment increased the parasitaemia, prevented the acute myocarditis and the sympathetic denervation without significant alteration of the myocardial parasitism. These results argue against a direct role for parasite-derived products and implicate the inflammatory cells in the denervation process. As previous studies in juvenile animals have discarded an essential role for radiosensitive cells, the macrophages remain as the possible effectors for the T. cruzi-induced neuronal damage.
Guerra
L B
LB
Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, MG, Brazil. lguerra@icb.ufmg.br
Andrade
L O
LO
Galvão
L M
LM
Macedo
A M
AM
Machado
C R
CR
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000469:parasitology / Q000517:prevention & control*; D002598:Chagas Cardiomyopathy / Q000150:complications / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006321:Heart / Q000294:innervation*; D006824:Hybridization, Genetic; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009205:Myocarditis / Q000469:parasitology / Q000517:prevention & control*; D018512:Parasitemia / Q000188:drug therapy; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000469:parasitology; D014349:Trypanosoma cruzi
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide