In situ expression of regulatory cytokines by heart inflammatory cells in Chagas' disease patients with heart failure.
Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi. The immune system plays an important role in the reduction of parasite load, but may also contribute to the development of lesions observed during the chronic phase of the disease. We analyzed cytokines produced by inflammatory heart cells in 21 autopsy samples obtained from patients with Chagas' disease divided according to the presence or absence of heart failure (HF). Left ventricular sections were analyzed by immunohistochemistry using antibodies against human IL-4, IFN-γ, TGF-β, TNF-α, and NOS2. In situ mRNA expression was quantified by a Low Density Array. The number of IFN-γ-positive cells was significantly higher than IL-4 positive cells. TNF-α, TGF-β and NOS2 were detected in 65%, 62% and 94% of samples respectively. There was an association between TNF-α-producing cells and the presence of HF. Subjects with HF presented higher levels of STAT4 mRNA, whereas FoxP3 and STAT6 levels were similar in the two groups. A Th1 cytokine pattern predominated in the cardiac inflammatory cell infiltrate of Chagas' disease patients associated with HF. High degree of fibrosis was associated with low NOS2 expression. These results support the idea that Th1 immune responses are involved in heart lesions of Chagas' disease patients.
Laboratory of Immunology, Institute of Biological Sciences, Federal University of Triângulo Mineiro, 38125-180 Uberaba, MG, Brazil.
Denise Bertulucci
DB
Rocha Rodrigues
Marlene Antonia
MA
dos Reis
Audrey
A
Romano
Sanívia Aparecida de Lima
SA
Pereira
Vicente de Paula Antunes
Vde P
Teixeira
Sebastião
S
Tostes
Virmondes
V
Rodrigues
D014355:Chagas Disease / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004719:Endomyocardial Fibrosis / Q000276:immunology / Q000473:pathology; D006333:Heart Failure / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II