Cytokine Profiles and Inflammatory Implications in Chagas Disease: Associations with Ventricular Function and...

The roles of cytokines and chemokines in the pathogenesis of Chagas cardiomyopathy (CC) have been proposed, yet their clinical significance with respect to conduction disturbances and left ventricular ejection fraction (LVEF) remains unclear.

The objective of this study was to analyze the associations between cytokine levels and systolic function, comparing patients with preserved and reduced ejection fractions. As a secondary objective, we evaluated whether differences were present in cytokine levels within the subgroup with preserved ejection fraction, depending on the presence or absence of intraventricular conduction disturbances.

We conducted an analytical cross-sectional study involving patients with Chagas disease and a healthy control group. Among patients with Chagas disease, those with preserved (>50%) and reduced (<35%) left ventricular ejection fraction (LVEF) were selected. The preserved-LVEF group included individuals with and without conduction disorders. Cytokines (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, IL-15, IL-17A, MCP-1, MIP1α, TNF-α, and IL-2) were quantified using a magnetic bead-based multiplex assay.

Forty-four patients with CD (26 men, 59%) and 14 seronegative controls were included. In the CD group, 50% (n = 22) had preserved LVEF (LVEF > 50%), and 50% (n = 22) had decreased LVEF (≤35%). No significant differences in cytokine concentrations were observed between patients with preserved and reduced LVEF for TNF-α (19.74 ± 8.32 vs. 22.23 ± 6.40 pg/mL; p = 0.189), IL-6 (2.17 ± 2.41 vs. 5.40 ± 6.40 pg/mL; p = 0.145), IL-2 (2.61 ± 1.05 vs. 2.97 ± 1.79 pg/mL; p = 0.481), MCP-1 (214.18 ± 96.99 vs. 183.83 ± 63.21 pg/mL; p = 0.481) and IFN-γ (9.04 ± 4.90 vs. 7.64 ± 3.78 pg/mL; p = 0.372). Within the subgroup with preserved LVEF (n = 22), those with conduction disorders (n = 10) exhibited higher levels of IL-10 (24.49 vs. 9.83 pg/mL; q = 0.009), IL-12p70 (13.20 vs. 9.02 pg/mL; q = 0.027), IL-2 (2.70 vs. 2.07 pg/mL; q = 0.023), IL-15 (7.09 vs. 3.36 pg/mL; q = 0.018), MIP1α (10.33 vs. 3.35 pg/mL; q = 0.014) and IFN-γ (10.83 vs. 7.25 pg/mL; q = 0.005), compared to those without conduction disorders (n = 12). Notably, patients with CD and preserved LVEF (>50%) without conduction disturbances presented cytokine profiles similar to those of seronegative healthy controls with LVEF ≥ 50%.

Elevated levels of specific cytokines were associated with conduction disturbances in patients with preserved LVEF. Despite this finding, a causal relationship cannot be established, and future studies are needed to explore their prognostic or therapeutic significance.