Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage

Back to the future in Chagas disease: from animal models to patient cohort studies, progress in immunopathogenesis research

“…Hardison et al (2006) reported similar findings in acutely infected CCR5-deficient C57Bl/6 mice, but these mice were not refractory to chronic inflammation. In contrast to their results, Medeiros et al (2009) recently reported that Met-RANTES ameliorated cardiac damage in mice chronically infected with the Colombian strain. Accordingly, Met-RANTES significantly decreased the numbers of intracardiac CD4 + T cells, without significantly affecting recruitment of CD8 + T and F4/80 + macrophages to the myocardium.…”

Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

“…43,44 In addition, a partial blockage of CC-chemokine receptor inhibitor (Met-RANTES) was shown to induce a reduction of the leukocyte influx modulated by T. cruzi followed by parasite load reduction and fibronectin deposition in the heart tissue. 45,46 Besides, CCL2 was also associated with the control of parasite burden, as well as with the increase of inflammatory infiltration and angiogenesis process induced by T. cruzi, 47,48 in particular by its essential role in recruiting monocytes to inflammatory foci.…”

Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease

“…In fact, the role of CCL5 in the recruitment of CCR5 + leukocytes has been reinforced by experiments that indicate that CCR5-deficient mice are more susceptible to T. cruzi infection after the reduction of macrophages and T-cell migration into the heart, especially during the early stages of infection (Machado et al 2005, Hardison et al 2006). Other evidence of this phenomenon is based on the partial blockage of the CC-chemokine receptor inhibitor (Met-RANTES), which induces a reduction in the leukocyte influx (modulated by T. cruzi), followed by a reduction in parasitaemia and a reduction in fibronectin deposition in the heart tissue (Marino et al 2004, Medeiros et al 2009). Simvastatin was able to drastically reduce CCL2/ MCP-1 and CCL5/RANTES, thereby culminating in a reduction in the migration of inflammatory cells into the cardiac organ; this effect could be associated with a good cardiac prognosis in experimental models.…”