期刊
PARASITOLOGY
卷 146, 期 7, 页码 914-927出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S003118201900009X
关键词
Angiotensin inhibitors; Chagas disease; clinical and experimental parasitology; renin-angiotensin system
类别
资金
- Fundacao do Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [APQ-01895-16, PPM-00077-18]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [303972/2017-3, 423594/2018-4]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]
Although leucocytes are targets of renin-angiotensin system (RAS) effector molecules and RAS-modulating drugs exert immunomodulatory effects, their impact on Trypanosoma cruzi infection remains poorly understood. By using the framework of a systematic review, we integrated the preclinical and clinical evidence to investigate the relevance of angiotensin-inhibiting drugs on T. cruzi infections. From a comprehensive and structured search in biomedical databases, only original studies were analysed. In preclinical and clinical studies, captopril, enalapril and losartan were RAS-modulating drugs used. The main in vitro findings indicated that these drugs increased parasite uptake per host cells, IL-12 expression by infected dendritic cells and IFN-gamma by T lymphocytes, in addition to attenuating IL-10 and IL-17 production by CD8 + T cells. In animal models, reduced parasitaemia, tissue parasitism, leucocytes infiltration and mortality were often observed in T. cruzi-infected animals receiving RAS-modulating drugs. In patients with Chagas' disease, these drugs exerted a controversial impact on cytokine and hormone levels, and a limited effect on cardiovascular function. Considering a detailed evaluation of reporting and methodological quality, the current preclinical and clinical evidence is at high risk of bias, and we hope that our critical analysis will be useful in mitigating the risk of bias in further studies.
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