IMMUNOENDOCRINE INTERACTIONS DURING LYMPHOCYTE MIGRATION IN HUMAN CHAGAS DISEASE

BERBERT L, PÉREZ AR, REVELLI S, BOTTASSO O, SAVINO W.

Foz do Iguacu

Congreso; XXXVI Congress of the Brasilian Society of Immunology and IV Section of Clinical Immunology; 2011

Sociedad Brasilera de Inmunologia

Text: Chagas Disease is an important public health burden in Americas. This disease is characterized by many physiological pathways, such as imunoneuroendocrine interactions that may modulate cytokines, chemokines and hormones expression (J Neuroimmunol,  235(1-2):84-90, 2011) which may lead to an imbalance on lymphocyte migration to inflammatory sites and myocarditis . In this work, we intend to evaluate T lymphocyte migratory potential from chronic chagasic patients with different clinical forms of cardiopaty, correlating these events to immunoendocrine alterations that occur during this phase of disease. By ELISA assays, we firstly observed that pro inflammatory cytokines/chemokines such as IFN- γ, TNF- alfa, IL-17 and IL-6, were higher expressed due to severity of chronic disease, as well as an increasing on its in vitro migratory potential over fibronectin was observed by Transwell® migration. We also observed an imbalance on Hypofisis-Pituitary-Adrenal (HPA) axis, where a decreasing of DHEA hormone leads to dirturbances on  circulating cortisol/DHEA ratio. As perspectives of this work, we also intend to analyse  gene expression profiles of migrated CD4+ and CD8+ lymphocytes, as it is known that cell migration is modulated by RNAm /microRNAs interactions.Methods and results: Chronic chagasic patients were grouped into indeterminate (ID)(n=16), Moderated (CARD)(n=16) and Severe (CARD sev) (n=16) cardiopaty degrees, as well as control healthy donors (Co). By ELISA assays we firstly observed that pro inflammatory cytokines/chemokines such as IFN- γ (10-13 pg/ml CARD sev,5 pg/ml Co) TNF- ALFA (29-37 pg/ml CARD sev, 3 pg/ml Co) IL-17 (30-45 pg/ml CARD sev, n.d. Co) and IL-6 (4-4.5 pg/ml CARD sev, 2-2.2 pg/ml Co) were higher expressed during chronic disease, and it was directly related to cardiopaty degrees, as well as an unbalance on Hypofisis-Pituitary-Adrenal (HPA) axis, where a decreasing of DHEA hormone leads to dirturbances on  circulating cortisol/DHEA ratio (3-3.5 AU CARD sev, 1-1.2 AU Co). We also observed by in vitro Transwell migration a tendency of T lymphocyte migratory potential over fibronectin, also related to cardiopaty degrees.Conclusion: Our first results demonstrated that neuroendocrine disturbances, correlated to a systemic inflammatory profile, may contribute to increase migratory potential of T lymphocytes to inflammatory sites and myocarditis genesis. Financial support: CNPq, CAPES, IOC.