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

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...

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Bibliographic Details
Published in:	Mediators of Inflammation Vol. 2014; no. 8; pp. 78 - 93
Main Authors:	Lannes-Vieira, Joseli, Britto, Constança, Moreira, Otacilio Cruz, Silva, Andrea Alice, Vilar-Pereira, Glaucia, Pereira, Isabela Resende, Sarmento, Ellen Diana Marinho
Format:	Journal Article
Language:	English
Published:	Cairo, Egypt Hindawi Limiteds 01-01-2014 Hindawi Publishing Corporation John Wiley & Sons, Inc Hindawi Limited
Subjects:	Animals Antibodies, Monoclonal - therapeutic use Chagas Disease - drug therapy Chagas Disease - metabolism Chagas' disease Female Flow Cytometry Health aspects Heart - drug effects Heart - parasitology Heart diseases Heart Diseases - drug therapy Heart Diseases - metabolism Identification and classification Immune response Immunohistochemistry Infliximab Interleukin-10 - metabolism Interleukin-17 - metabolism Mice Mice, Inbred C57BL Nitric Oxide - metabolism Physiological aspects Reverse Transcriptase Polymerase Chain Reaction Trypanosoma cruzi - pathogenicity Tumor necrosis factor Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - metabolism
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Summary:	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.
Bibliography:	Academic Editor: Christophe Chevillard
ISSN:	0962-9351 1466-1861
DOI:	10.1155/2014/798078