Rol del Factor de Necrosis Tumoral alfa en la miocarditis chagásica crónica

ANA ROSA PÉREZ

La Plata

Jornada; ISHR 2010 - XVIII Reunión Anual de la International Society for Heart Reserch; 2010

International Society for Heart Research - Latinoamerican Section

ROLE OF TNF-a  IN CHAGASIC MYOCARDITISPérez Ana Rosa.  Instituto de Inmunología, Facultad de Ciencias Médicas, UNR, Rosario, Argentina.  We previously observed during acute T. cruzi infection in TNF-R1+2 double knockout mice an absence of inflamatory infiltrates in heart in presence of numerous amastigote nests. Moreover, in vitro studies showed that T cell migration from infected mice and chagasic patients was enhanced by TNF- treatment, suggesting a role of this cytokine in the pathogenesis of chronic myocardial damage. To address this issue, we analyzed in a rat model of infection whether short treatment with Infliximab (Iab, TNF- blocker) affected the characteristics of chronic disease, including myocarditis. Iab was administered during the chronic phase for a period of 4 weeks (3 mg/kg/week), while control infected rats were treated with saline physiological solution. After treatment,  search for circulating parasites was unsuccessful but the presence of T. cruzi kDNA in heart tissue was detected in all infected groups, irrespective of treatment. Iab induced changes in the anti-parasite cytokine response, exemplified by an increase in the serum levels of IL-10 and TGF-a of the infected and Iab-treated group respect to the remaining groups (p < 0.05 in both cases). A clear attenuation of histological damage associated with a diminution of cardiac macrophages, CD8+ and CD4+ T cells and also TNF-a mRNA expression was observed in the infected Iab-treated animals compared to the infected non-treated group. It follows, that inhibition of TNF-a during a chronic period reduced myocarditis severity.