The online version of this article (doi:10.1186/s12879-017-2324-x) contains supplementary material, which is available to authorized users.
Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by heart failure and sudden death. Identifying which factors are involved in evolution and treatment response is actually challenging.
Thus, the aim of this work was to determine the Th1/Th17 (IL-6, IL-2, TNF, IL-17 and IFN-γ) and Th2 (IL-4 and IL-10) serum profile in Venezuelan Chagasic patients stratified according amiodarone treatment, hypertension and arrhythmias.
Sera from 38 chagasic patients were analyzed to determine the level of cytokines by Multiplexed Bead-Based Immunoassays. ANOVA test was applied to determine differences for each group. Additionally, a Linear Discriminant Analysis (LDA) was applied to observe the accuracy of different cytokines to discriminate between the groups.
The levels of several cytokines were significantly higher in the high-risk of sudden death and untreated group. LDA showed that IL-2, IFN-γ and IL-10 were the best cytokines for discriminating between high-risk of sudden death and untreated patients versus low-risk of sudden death, treated and control groups.
High IL-2 levels seem to identify patients with high-risk of sudden death and seems adequate as treatment efficacy marker. To our knowledge, this is the first report about the anti-inflammatory role of the amiodarone in Chagas disease, suggesting an inmunomodulatory effect that may be exploited as coadjutant therapy in chronic Chagas disease.
Additional file 1: Figure S1. One phase association fit curves for pattern curve data. Axes represent association between mean fluorescence (MFI) values obtained for different know cytokine with results expressed in pg/ml (y axis). Y=Y0 + (Plateau-Y0)*(1-exp.(-K*x)) equation was used for calculating cytokine concentration for patient samples. Figure S2. High producer frequencies for Lown stratified Chagasic patients. Bar graph shows the percentage of high producers for the different cytokines studied for Lown clinical scoring. Control high producer’s percentages is showed as dotted line and Chagasic frequencies (high & low SD risk) as bars. Threshold to determining high producers was calculated on ROC curve values for patients included in this group. Figure S3. High producer frequencies for blood pressure stratified Chagasic patients. Bar graph shows the percentage of high producers for the different cytokines studied for blood pressure clinical scoring. Control high producer’s percentages is showed as dotted line and Chagasic frequencies (normotensive & hypertensive) as bars. Threshold to determining high producers was calculated on ROC curve values for patients included in this group. Figure S3. High producer frequencies for amiodarone treatment stratified Chagasic patients. Bar graph shows the percentage of high producers for the different cytokines studied for blood pressure clinical scoring. Control high producer’s percentages is showed as dotted line and Chagasic frequencies (untreated & treated) as bars. Threshold to determining high producers was calculated on ROC curve values for patients included in this group. (XLSX 980 kb)12879_2017_2324_MOESM1_ESM.xlsx
Salazar R, Castillo-Neyra R, Tustin AW, Borrini-Mayori K, Naquira C, Levy MZ. Bed Bugs ( Cimex lectularius) as Vectors of Trypanosoma cruzi. AmJTrop Med Hyg. 2014;92(2):331–5. CrossRef
Mendoza IMF, Marques J, Misticchio F, Matheus A. Rodriguez, A. Ventricular tachycardia in Chagas heart disease. Ital Card. 1999;29:247–50.
Ribeiro AL, Cavalvanti PS, Lombardi F, Nunes Mdo C, Barros MV, Rocha MO;Prognostic value of signal-averaged electrocardiogram in Chagas disease. J Cardiovasc Electrophysiol 2008;19(5):502-509.
Guedes PM, Gutierrez FR, Silva GK, Dellalibera-Joviliano R, Rodrigues GJ, Bendhack LM, Rassi Jr A, Rassi A, Schmidt A, Maciel BC, et al. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas' disease. PLoS Negl Trop Dis. 2012;6(4):e1630. CrossRefPubMedPubMedCentral
Benaim G, Hernandez-Rodriguez V, Mujica-Gonzalez S, Plaza-Rojas L, Silva ML, Parra-Gimenez N, Garcia-Marchan Y, Paniz-Mondolfi A, Uzcanga G. In vitro anti-Trypanosoma cruzi activity of dronedarone, a novel amiodarone derivative with an improved safety profile. Antimicrob Agents Chemother. 2012;56(7):3720–5. CrossRefPubMedPubMedCentral
Gali WL, Sarabanda AV, Baggio JM, Ferreira LG, Gomes GG, Marin-Neto JA, Junqueira LF. Implantable cardioverter-defibrillators for treatment of sustained ventricular arrhythmias in patients with Chagas' heart disease: comparison with a control group treated with amiodarone alone. Europace. 2014;16(5):674–80. CrossRefPubMed
Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A, Jr., Rosas F, Villena E, Quiroz R, Bonilla R, Britto C, et al. Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy. N Engl J Med 2015;373(14):1295-1306.
Poveda C, Fresno M, Girones N, Martins-Filho OA, Ramirez JD, Santi-Rocca J, Marin-Neto JA, Morillo CA, Rosas F, Guhl F. Cytokine profiling in Chagas disease: towards understanding the association with infecting Trypanosoma cruzi discrete typing units (a BENEFIT TRIAL sub-study). PLoS One. 2014;9(3):e91154. CrossRefPubMedPubMedCentral
Gil Flores J GJE, Rodríguez Gómez G. Análisis Discriminante, vol. 12. Madrid, España: Editorial La Muralla; 2001.
Jones EM, Colley DG, Tostes S, Lopes ER, Vnencak-Jones CL, McCurley TL. A Trypanosoma cruzi DNA sequence amplified from inflammatory lesions in human chagasic cardiomyopathy. Trans Assoc Am Phys. 1992;105:182–9. PubMed
Higuchi Mde L, De Brito T, Martins Reis M, Barbosa A, Bellotti G, Pereira-Barreto AC, Pileggi F. Correlation between Trypanosoma cruzi parasitism and myocardial inflammatory infiltrate in human chronic chagasic myocarditis: Light microscopy and immunohistochemical findings. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 1993;2(2):101–6. CrossRef
Garcia S, Ramos CO, Senra JF, Vilas-Boas F, Rodrigues MM, Campos-de-Carvalho AC, Ribeiro-Dos-Santos R, Soares MB. Treatment with benznidazole during the chronic phase of experimental Chagas’ disease decreases cardiac alterations. Antimicrob Agents Chemother. 2005;49(4):1521–8. CrossRefPubMedPubMedCentral
Pereira IR, Vilar-Pereira G, Silva AA, Moreira OC, Britto C, Sarmento ED, Lannes-Vieira J. Tumor necrosis factor is a therapeutic target for immunological unbalance and cardiac abnormalities in chronic experimental Chagas' heart disease. Mediat Inflamm. 2014;2014:798078. CrossRef
Nogueira LG, Santos RH, Fiorelli AI, Mairena EC, Benvenuti LA, Bocchi EA, Stolf NA, Kalil J, Cunha-Neto E. Myocardial gene expression of T-bet, GATA-3, Ror-gammat, FoxP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: an essentially unopposed TH1-type response. Mediat Inflamm. 2014;2014:914326.
Reis DD, Jones EM, Tostes Jr S, Lopes ER, Gazzinelli G, Colley DG, McCurley TL. Characterization of inflammatory infiltrates in chronic chagasic myocardial lesions: presence of tumor necrosis factor-alpha+ cells and dominance of granzyme A+, CD8+ lymphocytes. AmJTrop Med Hyg. 1993;48(5):637–44.
Reis MM, Higuchi Mde L, Benvenuti LA, Aiello VD, Gutierrez PS, Bellotti G, Pileggi F. An in situ quantitative immunohistochemical study of cytokines and IL-2R+ in chronic human chagasic myocarditis: correlation with the presence of myocardial Trypanosoma cruzi antigens. Clin Immunol Immunopathol. 1997;83(2):165–72. CrossRefPubMed
Hak L, Mysliwska J, Wieckiewicz J, Szyndler K, Siebert J, Rogowski J. Interleukin-2 as a predictor of early postoperative atrial fibrillation after cardiopulmonary bypass graft (CABG). J Interf Cytokine Res. 2009;29(6):327–32. CrossRef
Cheng SM, Lin WH, Lin CS, Ho LJ, Tsai TN, Wu CH, Lai JH, Yang SP. Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone. Exp Biol Med. 2015;240(1):99–108. CrossRef
Ozbakis-Dengiz G, Halici Z, Akpinar E, Cadirci E, Bilici D, Gursan N. Role of polymorphonuclear leukocyte infiltration in the mechanism of anti-inflammatory effect of amiodarone. Pharmacological reports: PR. 2007;59(5):538–44. PubMed
Tanigaito Y, Sato K, Kitamura K, Suzuki A, Futase A, Shiga T, Hagiwara N. Abstract 15132: Amiodarone Treatments Improve the Inflammation in Heart Failure. Circulation. 2014;130(Suppl 2):A15132.
- Differential cytokine profiling in Chagasic patients according to their arrhythmogenic-status
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