title: Tumor necrosis factor is a therapeutic target for immunological unbalance and cardiac abnormalities in chronic experimental Chagas' heart disease.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Avenida Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Isabela Resende
authors.initials: IR
authors.lastname: Pereira
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Avenida Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Glaucia
authors.initials: G
authors.lastname: Vilar-Pereira
authors.affiliation: Departamento de Patologia, Universidade Federal Fluminense, 24033-900 Niterói, RJ, Brazil.
authors.forename: Andrea Alice
authors.initials: AA
authors.lastname: Silva
authors.affiliation: Laboratório de Biologia Molecular e Doenças Endêmicas, IOC/Fiocruz, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Otacilio Cruz
authors.initials: OC
authors.lastname: Moreira
authors.affiliation: Laboratório de Biologia Molecular e Doenças Endêmicas, IOC/Fiocruz, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Constança
authors.initials: C
authors.lastname: Britto
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Avenida Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Ellen Diana Marinho
authors.initials: ED
authors.lastname: Sarmento
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz/Fiocruz, Avenida Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Joseli
authors.identifier: 0000-0001-5503-6754
authors.initials: J
authors.lastname: Lannes-Vieira
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006321:Heart / Q000187:drug effects / Q000469:parasitology; D006331:Heart Diseases / Q000188:drug therapy* / Q000378:metabolism*; D007150:Immunohistochemistry; D000069285:Infliximab; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D000069285:Infliximab