immunology of infectious and parasitic diseases - XXXVII Congress ...

MODULATION OF IMMUNE RESPONSE AND CARDIOMYOCYTE
FUNCTION BY ZILEUTON DURING EXPERIMENTAL TRYPANOSOMA
CRUZI INFECTION
RONAN RICARDO SABINO ARAÚJO(PG) 1 ; DANILO ROMAN
CAMPOS(PhD) 1 ; ANDRÉIA BARROSO(IC) 1 ; FÁTIMA BRANT(PG) 1,2 ; LÍSIA
ESPER(PG) 1,2 ; ROSA MARIA ESTEVES ARANTES(PhD) 3 ; DANIELE DA
GLÓRIA SOUZA(PhD) 4 ; JADER DOS SANTOS CRUZ(PhD) 1 ; HERBERT
BERNARD TANOWITZ(PhD) 5 ; MAURO MARTINS TEIXEIRA(PhD) 1,2 ;
FABIANA SIMÃO MACHADO(PhD) 1,2
1 Departamentos de Bioquímica e Imunologia , 3 Patologia e 4 Microbiologia,
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, MG,
Brazil. 2 Departamento de Clínica Médica - Medicina Tropical e Infectologia,
Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo
Horizonte, MG, Brazil. 5 Departments of Pathology and Medicine, Albert Einstein
College of Medicine, Bronx, NY.
Introduction: The Chagas‟ disease is an illness highly neglected caused by
Trypanosoma cruzi parasite. The T. cruzi infection may lead a mega syndrome
and Chagasic cardiomyopathy development. Lipoxin A (LXA) is a modulator of
immune response, synthesized for 5-lipoxygenase (5-LO) activities, via
aracdonic acid pathway. Zileuton is a 5-LO inhibitor, which can modulate the
immune response through manipulation of 5-LO derived production. Here we
study the effects of Zileuton treatment on some parameters of immune
response and development of myocarditis during T. cruzi infection.
Methods: Mice C57BL/6 was infected with T. cruzi Y strain and treated with
Zileuton (30mg/Kg) via oral at different time points after infection. The
parasitemia was observed, and heart, spleen and liver were removed for mRNA
expression of cytokines and histological analysis. Cytokine levels were detected
in serum and splenic cells by ELISA and flow cytometry, respectively.
Results: We found reduced parasite load in mice treated with Zileuton
compared with untreated mice. Zileuton treatment also resulted in decreased
production of IL-12 and IFN-g detected in serum during the acute phase of
infection. Moreover there was decreased IFN-g mRNA levels in the heart and
spleen of treated mice. During the acute phase of infection, T CD4 + and T CD8 +
cells harvested from spleen of treated mice produced reduced levels of IFN-g
when compared with untreated mice. Additionally, we found reduced IL-6 and
IL-10 mRNA levels in spleen of treated mice. Furthermore, the Zileuton