Plasma Cytokine Expression Is Associated with Cardiac Morbidity in Chagas Disease

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.

Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas’ Heart Disease

“…Actually, IL-10-production by T-cells promotes T. cruzi control and protection from fatal acute myocarditis [45] and, thus, may concur to the beneficial effects of anti-TNF in chronic infection. More importantly, higher IL-10 expression was associated with better left ventricular ejection fraction and left ventricular diastolic diameter values in CD patients [5]. Our data support that anti-TNF therapy alters the inflammatory/regulatory balance in innate and adaptive immune effectors during chronic T. cruzi infection.…”

“…To our knowledge, this is the first description of a beneficial effect of anti-TNF therapy on major immunological features previously shown to parallel CCC [1–5]. In T. cruzi infection, anti-TNF therapy reduced acute cardiomyocyte lesion [12] and reversed chronic depressive-like behavior [21].…”

Chagas Disease: Still Many Unsolved Issues

“…Therefore, if defective local sensing occurs in CCC patients, strong local immune responses would clearly represent a detrimental factor in the induction of pathology, thus explaining the reported associations between high levels of cardiac dysfunction and genotypes associated with high reactivity [69, 70]. Furthermore, the inverse correlation observed in CCC patients between the intensity of electrocardiogram abnormalities and IL-10 plasma levels [59] reinforces this view. That is, to respond strongly when there is a gap in local T. cruzi control clearly represents a deleterious manner of dealing with the parasite.…”

La respuesta inmunitaria adaptativa en la infección crónica por Trypanosoma cruzi

“…Los linfocitos T CD8+ pueden participar en la patogenia a través de la citotoxicidad directa o mediante la producción de citocinas como TNF-α (RochaRodrigues, et al, 2012; Silverio, et al, 2012). En pacientes con mayor compromiso cardiaco se presentan altos niveles circulantes de TNF-α (Talvani, et al, 2004), los cuales se asocian con la progresión de la cardiopatía chagásica (Sousa, et al, 2014). Los linfocitos T infiltrantes en miocardiopatía crónica expresan receptores inhibitorios (CTLA-4 y PD-1) indicadores de agotamiento celular (Argüello, et al, 2012).…”