Enalapril prevents cardiac immune-mediated damage and exerts anti-Trypanosoma cruzi activity during acute phase of experimental Chagas disease G. DE PAULA COSTA, 1 R. R. SILVA, 2 M. C. PEDROSA, 1 V. PINHO, 4 W. G. DE LIMA, 1,2 M. M. TEIXEIRA, 3 M. T. BAHIA 1,2 & A. TALVANI 1,2 1 Departamento de CiÞncias Biológicas, Universidade Federal de Ouro Preto, Campus universitµrio, Ouro Preto, MG, Brazil, 2 Nfflcleo de Pesquisas em CiÞncias Biológicas, Universidade Federal de Ouro Preto, Campus universitµrio, Ouro Preto, MG, Brazil, 3 Departamento de Bioquímica e Imunologia, Instituto de CiÞncias Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, 4 Departamento de Morfologia, Instituto de CiÞncias Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil SUMMARY Chagas heart disease (CHD), caused by Trypanosoma cruzi infection, is a significant cause of morbidity and mortality in South and Central America. Enalapril, an angiotensin converting enzyme (ACE) inhibitor, is an important drug used to ameliorate heart functional capacity and its remod- elling in individuals presenting CHD. In this study, we evalu- ated the effects of enalapril on systemic and cardiac immune response during experimental acute CHD. C57BL ⁄ 6 mice infected with 50 trypomastigote forms of T. cruzi (Colom- bian strain) were treated daily with enalapril (25 mg ⁄ kg) and, after 30 days, a reduction in seric levels of IFN- gamma, TNF-alpha, CCL5 ⁄ RANTES and nitric oxide, but not in that of IL-10, was detected. This imbalance of cyto- kines reflects in a reduction of heart mononuclear infiltra- tion and in an increasing of cardiac mast cells. Enalapril also presents a new and interesting in vitro and in vivo anti- T. cruzi activity probably acting on parasite oxidative path- way via cytochrome-P450. Our data show that enalapril exerts an important anti-T. cruzi and anti-inflammatory activity during acute CHD reducing inflammatory cells and, possibly, preventing fibrotic process in the chronic phase. Nevertheless, further studies are still necessary to clarify the mechanisms by which this drug is acting on the parasites and on the immune pathways. Keywords cytokines, enalapril, heart inflammation, Trypanosoma cruzi INTRODUCTION Chagas cardiopathy is a multifactorial disease caused by Trypanosoma cruzi infection and characterized by a wide variety of inflammatory, functional and electrical alterations (1). Antiparasitic therapy with benznidazole or nifurtimox is ineffective when given to the symptomatic individuals in chronic stage of chagas cardiopathy. Then, to avoid cardiac failure, patients with a minimum symp- tom are conducted to a well controlled pharmacotherapy involving diuretic, digital, beta-blockers and ⁄ or inhibitor of angiotensin converting enzyme (ACE) (2). Angiotensin II is the product of ACE action which regu- lates vascular tone, stimulates the release of cytokines and chemokines, activates nuclear factor-kB (NF-kB), increases oxidant stress and suppress nitric oxide synthesis (3). Hence, the increase in ACE activity and ⁄ or concentrations of angiotensin II trigger and perpetuate the inflammation especially because it is possible to find ACE in many tissues of the body including the heart, vascular tissue, leucocytes, peripheral monocytes and others (3,4). Ena- lapril emerges as an ACE inhibitor designed to treat hyper- tension by blocking the conversion of angiotensin I into angiotensin II (5) and it is widely used in the treatment of cardiovascular diseases (e.g. heart failure and coronary artery diseases) and renal failure (6). And by its close rela- tionship with block of angiotensin II, ACE inhibitors have been clearly shown to exert anti-ischaemic action, inhibit thrombosis and platelet aggregation, improve endothelial function and vessel remodelling and express immune regulating and anti-inflammatory properties (7). Correspondence: AndrØ Talvani, Laboratório de doenÅa de Chagas, DECBI ⁄ NUPEB, Universidade Federal de Ouro Preto, ICEB II, Campus Morro do Cruzeiro, 35400-000 Ouro Preto, MG, Brazil (e-mail: talvani@nupeb.ufop.br). Disclosures: Authors and co-authors do not present any conflict of interest concerning this publication. Received: 26 July 2009 Accepted for publication: 26 October 2009 Parasite Immunology, 2010, 32, 202–208 DOI: 10.1111/j.1365-3024.2009.01179.x 202 Ó 2010 Blackwell Publishing Ltd