Abstract
The expression of immune response appears to be associated with morbidity in Chagas disease. However, the studies in this field have usually employed small samples of patients and statistical analyses that do not consider the wide dispersion of cytokine production observed in these patients. The aim of this study was to evaluate the plasma cytokine levels in well-defined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity. Patients infected with Trypanosoma cruzi (T. cruzi) were grouped as indeterminate (IND) and cardiac (CARD) forms ranging from 23 to 69 years of age (mean of 45.6±11.25). The IND group included 82 individuals, ranging from 24 to 66 years of age (mean of 39.6±10.3). The CARD group included 94 patients ranging from 23 to 69 years of age (mean of 48±12.52) presenting dilated cardiomyopathy. None of the patients have undergone chemotherapeutic treatment, nor had been previously treated for T. cruzi infection. Healthy non-chagasic individuals, ranging from 29 to 55 years of age (mean of 42.6±8.8) were included as a control group (NI). IND patients have a higher intensity of interleukin 10 (IL-10) expression when compared with individuals in the other groups. By contrast, inflammatory cytokine expression, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1β), proved to be the highest in the CARD group. Correlation analysis showed that higher IL-10 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Altogether, these findings reinforce the concept that a fine balance between regulatory and inflammatory cytokines represents a key element in the establishment of distinct forms of chronic Chagas disease.
Highlights
Chronic cardiomyopathy represents the most important and severe manifestation of human Chagas disease, eventually affecting approximately 20–30% of those in the chronic phase of the disease
Data analysis showed that the IND group presented significantly higher levels of interleukin 10 (IL-10), median of 22.91 (8.98–42.49), as compared to the CARD group, median of 9.93 (2.31–25.58) and the NI group, median of 5.26 (3.19–8.77) (P,0.0001) (Figure 1A)
In the CARD group, the expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-a) was significantly higher than IFN-c and interleukin 1 beta (IL-1b) (P,0.0001). This finding clearly shows that IL-10 is higher in the IND group, while IFN-c, TNF-a, and IL-6 are higher in the CARD groups, as compared to the NI group
Summary
Chronic cardiomyopathy represents the most important and severe manifestation of human Chagas disease, eventually affecting approximately 20–30% of those in the chronic phase of the disease. Epidemiological studies in endemic areas have shown that 2–5% of patients will evolve each year from the indeterminate to a clinical form of the disease [3]. While the balance between inflammatory and anti-inflammatory cytokines produced by circulating cells in patients with IND form leans towards to an anti-inflammatory profile, patients with chagasic cardiomyopathy seems to display a predominantly inflammatory environment [4,5,6,7,8]. Monocytes from IND patients produce higher levels of IL-10 than those from CARD patients [4,5,7]. The aim of this study was to evaluate the plasma cytokine levels in well-defined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity
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