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Mediators of Inflammation
Volume 2016, Article ID 3694714, 11 pages
Research Article

Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected Dogs

1Programa de Pós-Graduação em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil
2Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil
3Universidade Federal do Rio Grande do Norte Federal, Natal, RN, Brazil
4Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil
5Departments of Pediatrics & Pharmacology, Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada
6Programa de Pós-Graduação em Saúde e Nutrição, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil

Received 2 April 2016; Revised 14 July 2016; Accepted 4 August 2016

Academic Editor: Sandra Helena Penha Oliveira

Copyright © 2016 Guilherme de Paula Costa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain of T. cruzi and grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. After 14 months of infection, hearts were excised and processed for qPCR analysis of Th1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), Th2 (CCL1, CCL17, CCL24, and CCL26), Th17 (CCL20) CKs, Th1 (CCR5, CCR6, and CXCR3), and Th2/Th17 (CCR3, CCR4, and CCR8) CKR, as well as IL-17. T. cruzi infection increases CCL1, CCL2, CCL4, CCL5, CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6, and CXCR3. Our data reveal an immune modulatory effect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection.