Article
Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients
Registro en:
GUEDES, Paulo Marcos Matta; et al. Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients. PLoS Negl Trop Dis., v.10, n.4, 18p, e0004669. Apr. 2016.
1935-2727
10.1371/journal.pntd.0004669
1935-2735
Autor
Guedes, Paulo Marcos Matta
Andrade, Cléber Mesquita de
Nunes, Daniela Ferreira
Pereira, Nathalie de Sena
Queiroga, Tamyres Bernadete Dantas
Coelho, George Luiz Lins Machado
Nascimento, Manuela Sales Lima
Matta, Maria Adelaide Do Valle
Câmara, Antônia Cláudia Jácome da
Chiari, Egler
Galvão, Lúcia Maria da Cunha
Resumen
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 realtime
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 lowermRNA
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.