Unraveling the cytokine profile in acute Chagas disease in the Brazilian Amazon: Insights before and after treatment

Abstract

Chagas disease (CD) is a neglected anthropozoonosis caused by Trypanosoma cruzi, with the oral route standing out as the primary cause for the increase in acute cases in the Brazilian Amazon and a key factor in the increase of acute cases. Despite this, the immune response in affected individuals remains minimally explored in humans. This longitudinal study aimed to characterize the serum cytokine profile in patients with acute CD before and after treatment. Participants were recruited from several municipalities in the state of Amazonas, and individuals with chronic inflammatory diseases were excluded. The cytokines IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17α, TNF-α, and IFN-γ were analyzed. From 2017 to 2022, 35 patients and 14 controls were included (mean age 46.3 ± 17.8 years; 57.1% male; 74.3% from oral transmission outbreaks). Twenty-five patients (71.4%) were successfully followed up, despite logistical challenges. Elevated levels of all cytokines were found in acute-phase patients before treatment, indicating an effective immune activation. After an average of 12 months post-treatment, significant reductions were observed in IL-6 (p < 0.001), TNF-α (p = 0.011), IFN-γ (p < 0.001), and IL-10 (p = 0.015). IL-2 showed strong correlations with IL-1α and IL-17α in the acute phase (r = 0.91 and 0.95). Post-treatment cytokine profiles resembled those of the control group, suggesting treatment efficacy in modulating inflammation. IL-17α, IL-10, and IL-2 maintained an interesting pattern after treatment. Cardiac MRI revealed myocardial injury by late gadolinium enhancement (LGE) in 27.3% of pre-treatment and 33.3% of post-treatment patients. IL-1α, IL-17α, and IL-4 had moderate negative correlations (r=–0.36 to –0.67) with LGE. These results highlight the importance of monitoring the inflammatory response in the long term, as well as the observed cytokine modulation, which reinforces the hypothesis of not only a favorable acute immune response but also a sustained long-term clinical improvement following treatment.