title: Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals.
abstract: Understanding the pathogenic mechanisms in chronic Chagas disease, a major cause of morbidity and mortality in Latin America, is essential for the design of rational therapeutic strategies. In this paper we show that the development of Chagas disease is a consequence of a long-term and complex relationship between parasite persistence and maladapted homeostatic mechanisms in the host which leads to pathologic changes. We performed a retrospective study on 50 patients with chronic Chagas disease and 50 healthy control individuals. The specific immune response was detected by ELISA and IHA tests using autochthonous antigens, inflammatory process with the cytokine tumour necrosis factor (TNF)-alpha and nitric oxide (NO), and antioxidant protection with glutathione peroxidase and superoxide dismutase (SOD) levels. We developed generalised linear modelling procedures to assess simultaneously which explanatory variables and/or their interactions better explained disease severity in patients. Our results show the existence of a strong relationship between anti-Trypanosoma cruzi levels and chronic Chagas disease (P<0.0001). Taken together, the statistical data indicate both cumulative and complementary effects, where the increase in TNF-alpha (P=0.004) and NO (P=0.005) levels correlated with a reduction in glutathione peroxidase (P=0.0001) and SOD (P=0.01) levels drives the disease pathology in chronically infected patients. Our findings may have important implications for understanding host susceptibility to develop severe chronic infectious disease. In addition we show putative targets for the design of new therapeutic strategies to prevent disease progression, considering both specific treatment against the aetiological agent and modulation of the different immunopathological reactions in chronically infected individuals with chronic Chagas disease.
authors.affiliation: Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, 13 Sur 2901 Col. Volcanes, C.P. 72000, Pue., Puebla, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pérez-Fuentes
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Guégan
authors.forename: Christian
authors.initials: C
authors.lastname: Barnabé
authors.forename: Aurelio
authors.initials: A
authors.lastname: López-Colombo
authors.forename: Hilda
authors.initials: H
authors.lastname: Salgado-Rosas
authors.forename: Enrique
authors.initials: E
authors.lastname: Torres-Rasgado
authors.forename: Bernardo
authors.initials: B
authors.lastname: Briones
authors.forename: Mónica
authors.initials: M
authors.lastname: Romero-Díaz
authors.forename: Judith
authors.initials: J
authors.lastname: Ramos-Jiménez
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Sánchez-Guillén
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis; D000975:Antioxidants / Q000378:metabolism*; D016022:Case-Control Studies; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood*; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006790:Host-Parasite Interactions; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D012189:Retrospective Studies; D013482:Superoxide Dismutase / Q000097:blood; D014349:Trypanosoma cruzi / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000953:Antigens, Protozoan; D000975:Antioxidants; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase