Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients.
Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease.
Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Natal, Brazil.
Paulo Marcos Matta
PM
Guedes
Department of Biomedical Sciences, University of Rio Grande do Norte State, Rio Grande do Norte, Mossoró, Brazil.
Cléber Mesquita
CM
de Andrade
Department of Parasitology, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, Brazil.
Daniela Ferreira
DF
Nunes
Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Natal, Brazil.|Department of Parasitology, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, Brazil.
Nathalie
N
de Sena Pereira
Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Natal, Brazil.
Tamyres Bernadete Dantas
TB
Queiroga
School of Medicine, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
George Luiz Lins
GL
Machado-Coelho
Ribeirão Preto Medical School, University of São Paulo, São Paulo, Ribeirão Preto, Brazil.
Manuela Sales Lima
MS
Nascimento
Laboratory of Cellular Ultrastructure, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
Maria Adelaide
MA
Do-Valle-Matta
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
Antônia Cláudia Jácome
AC
da Câmara
Department of Parasitology, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, Brazil.
Egler
E
Chiari
Department of Parasitology, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, Brazil.
Lúcia Maria da Cunha
LM
Galvão
D000328:Adult; D000368:Aged; D014355:Chagas Disease / Q000150:complications* / Q000401:mortality* / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology* / Q000401:mortality*; D016019:Survival Analysis
D016207:Cytokines; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II