Could angiotensin-modulating drugs be relevant for the treatment of Trypanosoma cruzi infection? A systematic review of preclinical and clinical evidence

Souza-Silva, T. G. and Diniz, L. F. and Mazzeti, A. L. and Mendonca, A. A. S. and Goncalves, R. V. and Novaes, R. D.

Parasitology (2019) 146: 914–927

DOI: 10.1017/S003118201900009X

Abstract

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-P 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.

Citation

Souza-Silva, T. G., Diniz, L. F., Mazzeti, A. L., Mendonca, A. A. S., Goncalves, R. V., & Novaes, R. D. (2019). Could angiotensin-modulating drugs be relevant for the treatment of Trypanosoma cruzi infection? A systematic review of preclinical and clinical evidence. Parasitology, 146(7), 914–927. https://doi.org/10.1017/S003118201900009X cytokines, animals, animal models, man, therapeutics, therapy, mortality, in vitro, human diseases, death rate, Trypanosoma, infections, parasites, parasitoses, protozoal infections, T lymphocytes, antiviral agents, cardiovascular system, circulatory system, trypanosomiasis, Protozoa, protozoal diseases, Animal Models of Human Diseases [VV400], T cells, interferon-gamma, parasitic diseases, parasitic infestations, parasitosis, Protozoan, Helminth and Arthropod Parasites of Humans [VV220], parasitology, trypanosomosis, interleukin 10, interleukin 12, Human Immunology and Allergology [VV055], interleukins, leucocytes, leukocytes, white blood cells, Trypanosoma cruzi, angiotensin, CD8, CD8 antigens, Chagas’ disease, dendritic cells, immunological factors, interferons

Keywords

• cytokines
• animals
• animal models
• man
• therapeutics
• therapy
• mortality
• in vitro
• human diseases
• death rate
• Trypanosoma
• infections
• parasites
• parasitoses
• protozoal infections
• T lymphocytes
• antiviral agents
• cardiovascular system
• circulatory system
• trypanosomiasis
• Protozoa
• protozoal diseases
• Animal Models of Human Diseases [VV400]
• T cells
• interferon-gamma
• parasitic diseases
• parasitic infestations
• parasitosis
• Protozoan
• Helminth and Arthropod Parasites of Humans [VV220]
• parasitology
• trypanosomosis
• interleukin 10
• interleukin 12
• Human Immunology and Allergology [VV055]
• interleukins
• leucocytes
• leukocytes
• white blood cells
• Trypanosoma cruzi
• angiotensin
• CD8
• CD8 antigens
• Chagas’ disease
• dendritic cells
• immunological factors
• interferons