Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

D'avila, Daniela A; Guedes, Paulo M. M.; Castro, Ana Maria de; Gontijo, Eliane Dias; Chiari, Égler; Galvao, L. M. C.

doi:10.1590/s0074-02762009000100015

Cited by 34 publications

(17 citation statements)

References 32 publications

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“…The cultures of PBMC from patients with moderate/severe cardiomyopathy produced higher IFN-γ and TNF-α, and lower IL-10 levels than those observed in PBMC culture from free/mild cardiomyopathy patients, which is in accordance with previous reports by other researchers [1], [7], [9]. An imbalance in the production of cytokines IFN-γ and IL-10 was also observed in the present study, assaying these cytokines in the sera from chronic cardiac Chagas' disease patients: This imbalance has been implicated in the pathogenesis of Chagas heart disease [1], [7], [34]. Production of more IFN-γ and less IL-10 in cardiac patients supposedly results in efficient control of parasites replication but with more lesions to myocardium [5].…”

Section: Discussionsupporting

confidence: 93%

Deficient Regulatory T Cell Activity and Low Frequency of IL-17-Producing T Cells Correlate with the Extent of Cardiomyopathy in Human Chagas' Disease

et al. 2012

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BackgroundMyocardium damage during Chagas' disease results from the immunological imbalance between pro- and production of anti-inflammatory cytokines and has been explained based on the Th1–Th2 dichotomy and regulatory T cell activity. Recently, we demonstrated that IL-17 produced during experimental T. cruzi infection regulates Th1 cells differentiation and parasite induced myocarditis. Here, we investigated the role of IL-17 and regulatory T cell during human Chagas' disease.Methodology/Principal FindingsFirst, we observed CD4+IL-17+ T cells in culture of peripheral blood mononuclear cells (PBMC) from Chagas' disease patients and we evaluated Th1, Th2, Th17 cytokine profile production in the PBMC cells from Chagas' disease patients (cardiomyopathy-free, and with mild, moderate or severe cardiomyopathy) cultured with T. cruzi antigen. Cultures of PBMC from patients with moderate and severe cardiomyopathy produced high levels of TNF-α, IFN-γ and low levels of IL-10, when compared to mild cardiomyopathy or cardiomyopathy-free patients. Flow cytometry analysis showed higher CD4+IL-17+ cells in PBMC cultured from patients without or with mild cardiomyopathy, in comparison to patients with moderate or severe cardiomyopathy. We then analyzed the presence and function of regulatory T cells in all patients. All groups of Chagas' disease patients presented the same frequency of CD4+CD25+ regulatory T cells. However, CD4+CD25+ T cells from patients with mild cardiomyopathy or cardiomyopathy-free showed higher suppressive activity than those with moderate and severe cardiomyopathy. IFN-γ levels during chronic Chagas' disease are inversely correlated to the LVEF (P = 0.007, r = −0.614), while regulatory T cell activity is directly correlated with LVEF (P = 0.022, r = 0.500).Conclusion/SignificanceThese results indicate that reduced production of the cytokines IL-10 and IL-17 in association with high levels of IFN-γ and TNF-α is correlated with the severity of the Chagas' disease cardiomyopathy, and the immunological imbalance observed may be causally related with deficient suppressor activity of regulatory T cells that controls myocardial inflammation.

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Section: Discussionsupporting

confidence: 93%

Deficient Regulatory T Cell Activity and Low Frequency of IL-17-Producing T Cells Correlate with the Extent of Cardiomyopathy in Human Chagas' Disease

et al. 2012

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“…This fact is of interest, because in these patients, an imbalance in this response could drive disease progression toward a symptomatic/determinate form. Although the present results are in agreement with previous studies, 68,69 the relation between IFN‐γ, TNF‐α, IL‐10, and IL‐4 is controversial, because while some studies showed high concentrations of IFN‐γ and TNF‐α, with low concentrations of IL‐10 and Il‐4 associated with ChHD, 70–74 other studies have reported no difference in cytokine production between the chronic forms of the disease 75,76 …”

Section: Discussionsupporting

confidence: 88%

The Relationship between Heart Rate Variability and Serum Cytokines in Chronic Chagasic Patients with Persistent Parasitemia

Llaguno

Pertili

Silva

et al. 2011

Pacing Clinical Electrophis

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“…In fact, an association between certain IL10 genotypes and humoral and cellular immunity has been reported, which suggests that epistasis between IL‐10 and MHC could underlie the susceptibility/resistance to CD (39). Nevertheless, similar levels of IL‐10 have been detected in the serum of asymptomatic, cardiomyopathic and non‐infected individuals with T. cruzi (40). Thus, the lack of efficient regulation of IL‐10 in patients with cardiomyopathy could contribute to cardiac immunopathology.…”

Section: Discussionmentioning

confidence: 76%

Interleukin 4, interleukin 4 receptor‐α and interleukin 10 gene polymorphisms in Chagas disease

Flórez

Martı́n

González

2011

Parasite Immunology

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In this study, we investigated the association between single-nucleotide polymorphisms (SNPs) of the interleukin-4 (IL4), interleukin-4 receptor-α (IL4RA) and interleukin-10 (IL10) genes with the development of chagasic heart disease. This study included 260 patients from Colombia who were serologically positive for Trypanosoma cruzi antigens (cardiomyopathic, n=130; asymptomatic, n=130). Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism or sequence-specific primer methods. We found statistically significant differences in the distribution of the IL4RA +148 AA (P=0·025, OR=1·89, CI=1·04-3·43) genotype when comparing asymptomatic and symptomatic patients. No statistically significant differences in the genotype and allele frequency of IL4 and IL10 gene polymorphisms between symptomatic and asymptomatic patients were observed. Our experimental evidence suggests that the IL4RA +148 AA genotype has a weak association with the development of chagasic cardiomyopathy in the population under study.

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Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

Cited by 34 publications

References 32 publications

Deficient Regulatory T Cell Activity and Low Frequency of IL-17-Producing T Cells Correlate with the Extent of Cardiomyopathy in Human Chagas' Disease

Deficient Regulatory T Cell Activity and Low Frequency of IL-17-Producing T Cells Correlate with the Extent of Cardiomyopathy in Human Chagas' Disease

The Relationship between Heart Rate Variability and Serum Cytokines in Chronic Chagasic Patients with Persistent Parasitemia

Interleukin 4, interleukin 4 receptor‐α and interleukin 10 gene polymorphisms in Chagas disease

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