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Elevated concentrations of CCL2 and tumor necrosis factor-alpha in chagasic cardiomyopathy
André Talvani1, Manoel O C Rocha, Lucíola S Barcelos
1Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte Mg Brasil.
Insights
Tumor necrosis factor-alpha (TNF-alpha) and CCL2 levels in Chagas disease patients correlate with heart dysfunction. Measuring TNF-alpha may identify patients needing further treatment for heart failure.
Area of Science:
- Cardiology
- Immunology
- Infectious Diseases
Background:
- Chronic myocarditis is a key pathology in Chagas disease morbidity.
- Cardiac dysfunction is a significant complication of chronic Chagasic cardiomyopathy.
Purpose of the Study:
- To evaluate plasma concentrations of inflammatory markers and brain natriuretic peptide (BNP) in patients with varying clinical forms of chronic Chagasic cardiomyopathy.
- To determine the correlation between these markers and the degree of cardiac dysfunction.
- To assess the production of inflammatory markers by peripheral blood mononuclear cells.
Main Methods:
- Plasma samples from patients with Chagas disease were analyzed for CCL2, CCL3, tumor necrosis factor (TNF)-alpha, and BNP.
- Peripheral blood mononuclear cells (PBMCs) were stimulated to assess cytokine production.
- Statistical analysis correlated protein levels with clinical severity and heart function parameters.
Main Results:
- Elevated plasma concentrations of TNF-alpha, CCL2, and BNP were observed in patients with more severe Chagas disease.
- A strong correlation was found between these protein levels, particularly TNF-alpha, and the degree of heart dysfunction.
- Patients with chagasic cardiomyopathy showed increased TNF-alpha and CCL2 production by PBMCs compared to healthy individuals.
Conclusions:
- Plasma TNF-alpha levels are excellent predictors of heart failure in Chagas disease patients.
- Elevated TNF-alpha and CCL2 in plasma are linked to cardiac dysfunction severity.
- Spontaneous TNF-alpha and CCL2 production by PBMCs reflects both cardiac dysfunction and cardiac inflammation in Chagas disease.
- Measuring TNF-alpha could aid in identifying patients who may benefit from targeted interventions.
Abstract:
Chronic myocarditis is the main pathological finding associated with Chagas disease-related morbidity. Concentrations of CCL2, CCL3, tumor necrosis factor (TNF)-alpha, and brain natriuretic peptide (BNP) were evaluated in plasma samples obtained from patients with different clinical forms of chronic chagasic cardiomyopathy. Patients with more-severe Chagas disease had elevated plasma concentrations of TNF-alpha, CCL2, and BNP, and there was a good correlation between levels of these proteins (especially TNF-alpha ) and the degree of heart dysfunction. Indeed, TNF-alpha level was an excellent predictor of heart failure. Peripheral blood mononuclear cell samples obtained from patients with mild or severe chagasic cardiomyopathy produced greater amounts of TNF-alpha and CCL2 than did those obtained from noninfected individuals. The elevation of TNF-alpha and CCL2 levels in the plasma of patients appears to be secondary to the degree of heart dysfunction, whereas spontaneous production of TNF-alpha and CCL2 by mononuclear cells is secondary not only to heart dysfunction, but also to the underlying inflammation in the heart of chagasic patients. Measurement of the TNF-alpha level could be a useful tool in the identification of patients with heart dysfunction who may benefit from further investigation and treatment.
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