title: TNF blockade aggravates experimental chronic Chagas disease cardiomyopathy.
abstract: Chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi, is an inflammatory dilated cardiomyopathy associated with increased circulating levels of TNF-alpha. We investigate whether TNF blockade with Etanercept during the chronic phase of T. cruzi infection could attenuate experimental CCC development. The effect of Etanercept was evaluated after 11 months of T. cruzi infection on survival, parasitism, left ventricular function, intensity of myocarditis, fibrosis, and left ventricular mRNA expression of cytokines and TNF-alpha-induced genes. Left ventricular function was significantly reduced in treated animals as compared to infected untreated animals. Blood and cardiac parasitism as well as survival rate were not altered with Etanercept treatment. Inflammatory infiltrates were located predominantly in the subendocardic region in treated animals, whereas in untreated animals inflammation was scattered throughout the myocardium. Left ventricular mRNA IL-10 expression was significantly higher, and iNOS, significantly lower in treated than in untreated animals. mRNA expression of TNF-alpha, IFN-gamma, TGF-beta, A20 and ANP was similar in both groups. Our results suggest that TNF-alpha/LT-alpha blockade with Etanercept enhances left ventricular dysfunction in T. cruzi-induced chronic cardiomyopathy and the absence of TNF signaling may be deleterious to the failing heart in Chagas disease cardiomyopathy.
authors.affiliation: Heart Institute (InCor), University of São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Angelina M B
authors.initials: AM
authors.lastname: Bilate
authors.forename: Vera M
authors.initials: VM
authors.lastname: Salemi
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Ramires
authors.forename: Thales
authors.initials: T
authors.lastname: de Brito
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
authors.forename: Simone G
authors.initials: SG
authors.lastname: Fonseca
authors.forename: Kellen C
authors.initials: KC
authors.lastname: Faé
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Martins
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Silva
authors.forename: Charles
authors.initials: C
authors.lastname: Mady
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D000818:Animals; D001835:Body Weight; D002598:Chagas Cardiomyopathy / Q000235:genetics / Q000276:immunology*; D006224:Cricetinae; D004452:Echocardiography / Q000379:methods; D000068800:Etanercept; D005260:Female; D006321:Heart / Q000033:anatomy & histology; D007074:Immunoglobulin G / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000276:immunology; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D007074:Immunoglobulin G; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; D000068800:Etanercept