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Inflammation"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. 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.<jats:italic>Aim of the Study<\/jats:italic>. To challenge the hypothesis that TNF plays a key role in<jats:italic>Trypanosoma cruzi<\/jats:italic>-induced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronically<jats:italic>T. cruzi<\/jats:italic>-infected C57BL\/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas\u2019 heart disease.<jats:italic>Results<\/jats:italic>. Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFN<jats:italic>\u03b3<\/jats:italic>levels; diminished the frequency of IL-17A<jats:sup>+<\/jats:sup>but increased IL-10<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T-cells; reduced TNF<jats:sup>+<\/jats:sup>but augmented IL-10<jats:sup>+<\/jats:sup>Ly6C<jats:sup>+<\/jats:sup>and F4\/80<jats:sup>+<\/jats:sup>cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFN<jats:italic>\u03b3<\/jats:italic>-producing VNHRFTLV-specific CD8<jats:sup>+<\/jats:sup>T-cells in spleen and reduced the number of perforin<jats:sup>+<\/jats:sup>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.<jats:italic>Conclusions<\/jats:italic>. Our data support that TNF is a crucial player in the pathogenesis of Chagas\u2019 heart disease fueling immunological unbalance which contributes to cardiac abnormalities.<\/jats:p>","DOI":"10.1155\/2014\/798078","type":"journal-article","created":{"date-parts":[[2014,7,23]],"date-time":"2014-07-23T22:25:58Z","timestamp":1406154358000},"page":"1-16","source":"Crossref","is-referenced-by-count":50,"title":["Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas\u2019 Heart Disease"],"prefix":"10.1155","volume":"2014","author":[{"given":"Isabela Resende","family":"Pereira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es, Instituto Oswaldo Cruz\/Fiocruz, Avenida Brasil 4365, 21045-900 Rio de Janeiro, RJ, 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