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Mediators of Inflammation
Volume 2014, Article ID 798078, 16 pages
Research Article

Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas’ Heart Disease

1Laboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Avenida Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brazil
2Departamento de Patologia, Universidade Federal Fluminense, 24033-900 Niterói, RJ, Brazil
3Laboratório de Biologia Molecular e Doenças Endêmicas, IOC/Fiocruz, 21045-900 Rio de Janeiro, RJ, Brazil

Received 14 April 2014; Revised 24 June 2014; Accepted 26 June 2014; Published 22 July 2014

Academic Editor: Christophe Chevillard

Copyright © 2014 Isabela Resende Pereira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Chagas disease (CD) is characterized by parasite persistence and immunological unbalance favoring systemic inflammatory profile. Chronic chagasic cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and frequently progresses to heart failure. Aim of the Study. To challenge the hypothesis that TNF plays a key role in Trypanosoma cruzi-induced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronically T. cruzi-infected C57BL/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas’ heart disease. Results. Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFNγ levels; diminished the frequency of IL-17A+ but increased IL-10+ CD4+ T-cells; reduced TNF+ but augmented IL-10+ Ly6C+ and F4/80+ cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFNγ-producing VNHRFTLV-specific CD8+ T-cells in spleen and reduced the number of perforin+ cells infiltrating the myocardium. Importantly, Infliximab reduced the frequency of mice afflicted by arrhythmias and second degree atrioventricular blocks and decreased fibronectin deposition in the cardiac tissue. Conclusions. Our data support that TNF is a crucial player in the pathogenesis of Chagas’ heart disease fueling immunological unbalance which contributes to cardiac abnormalities.