Circulating cytokine levels in Chagas patients with and without dilated cardiomyopathy

Abstract

Dilated cardiomyopathy (DC) represents the most severe manifestation that affects ≈30% of individuals along 10-30 years after T. cruzi infection. To study the underlying mechanisms, circulating levels of different cytokines/chemokines were investigated in patients with DC or not (NC) and compared with healthy control donors (C).Chagas´ patients were recruited by the Cardiogenetic Center, Ramos Mejía Hospital, Bs. As., after signing the informed consent approved by the local Ethics Committee. All patients came from northwestern Argentina and southern Bolivia. No patient presented another etiology of dilated cardiomyopathy except Chagas. Enrolled patients were submitted to a standard follow up and clinical treatment. The NC group (n=22) included asymptomatic individuals, with ejection fraction (EF) more than 50 % and DC group (n=22) showed EF less than 35%. Normal healthy volunteers showing negative serological tests for the infection were included as the (C) group (n=14). Fasting plasma levels of IFNγ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1alpha/CCL3, TNFalpha and IL-2 were assessed using a Magnetic Bead Multiplex Assay in a Magpix® equipment (Merck Millipore). Concentrations were determined using the xPONENT software version 4.2.Our results showed that: 1- DC, in contrast to NC, had higher levels of TNFalpha than C (p: 0.010), 2- IL-6 concentration increased in DC with respect to NC (p: 0.033), 3- NC showed a trend to higher MCP-1 levels respect to DC (p: 0.119), 4-no differences were observed in the rest of the analyzed cytokines. These data suggest that IL-17A producing cells (IL3 and Th17) and INF-γ producers (NK, Tc, Th1 cells) have a little contribution in this phase of the disease. The present observations agree with the similar levels of IL-2, IL-12p70 and IL-15 found in all groups. In contrast, IL-6 and TNFalpha, likely derived from monocytes/macrophages, would contribute to cardiac inflammation and dysfunction in Chagas disease.