TNF blockade aggravates experimental chronic Chagas disease cardiomyopathy

Macrophage Depletion in Hypertensive Rats Accelerates Development of Cardiomyopathy

“…14 However, blocking of TNF-a has paradoxically resulted in worsening of experimental chronic Chagas disease-mediated cardiomyopathy, 15 which is similar to our observations. Third, macrophagedepleted hearts showed abundant T-lymphocyte infiltration.…”

TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-α blockade

“…Recently, TNF-α blockade has been shown to decrease necrotic areas in the spleen during acute T. cruzi infection (Andrade et al 2008). Conversely, treatment with Etanercept (soluble human TNFR2/p75 that binds TNF-α and lymphotoxin α) aggravated chronic chagasic cardiomyopathy in hamsters, leading to the claim that the absence of TNF-α signaling may be deleterious to the failing heart in Chagas disease cardiomyopathy (Bilate et al 2007). This apparent paradox emphasizes the need for an understanding of the modes of action and the limiting factors of emerging novel therapeutic tools that target TNF-α (Wong et al 2008).…”

Chagas disease cardiomyopathy: current concepts of an old disease

“…In order to test this, we used the hamster model for CCC (RAMIREZ et al, 1994;BILATE et al, 2003) to evaluate whether TNF-α blockade could attenuate disease progression. To our surprise, blocking TNF-α with a soluble TNF-α receptor (Etanercept) during the chronic phase of T. cruzi infection worsened CCC, as shown by impaired cardiac function, a hallmark of human CCC (BILATE et al, 2007). Severity of cardiomyopathy was not due to increased tissue or blood parasitism, direct drug toxicity on intact myocardium, increased myocardial fibrosis, or increased myocarditis and inflammatory cytokine expression in the heart.…”