Immunoendocrine interactions during lymphocyte migration in human Chagas Disease

BERBERT LR; PÉREZ AR; MANARIN R; GONZÁLEZ FB; PETRUCCI J; BELOSCAR J; BOTTASSO OA; SAVINO W

Campos de Jordao

Congreso; XXXVII Congress of the Brazilian society of immunology.; 2012

Brazilian society of immunology

Chagas Disease remains a public health issue in Americas. In the pathological processes seen in patients, we found changes in imunoneuroendocrine interactions, which might be related to an imbalance in lymphocyte migration to inflammatory sites. We evaluated T lymphocyte migratory responses from chagasic patients with different forms of cardiopathy, correlating these events to immunoendocrine alterations that occur during chronic disease. We first observed that pro-inflammatory cytokines were more expressed in parallel with the severity of disease. Additionally, we found an imbalance on Hypothalamus-Pituitary-Adrenal axis, where a decreasing of DHEA hormone results in changes of circulating cortisol/DHEA ratio. Also in parallel, we found an enhanced migratory response over fibronectin, CXCL12 and TNF-α, as well as with Cortisol and DHEA pre-treatment. These results suggest that endocrine disturbances, correlated to an inflammatory profile, may contribute to increase migratory potential of T lymphocytes to inflammatory sites and myocarditis.  Methods and results: Chronic chagasic patients were grouped into INDETERMINATE (n=18), MODERATE (n=18) and SEVERE (n=15) cardiopathy degrees, as well as CONTROL donors (n=7). By ELISA assays we observed that pro-inflammatory molecules such as IFN-γ (10-13 pg/ml SEV vs 5 pg/ml CT), TNF-α (29-37 pg/ml SEV vs 3 pg/ml CT), IL-17 (30-45 pg/ml SEV vs n.d. CT) and IL-6 (4-4.5 pg/ml SEV vs 2-2.2 pg/ml CT) were higher expressed during chronic disease, and it was directly related to cardiopathy degrees, as well as an imbalance on Hypothalamus-Pituitary-Adrenal axis, where a decreasing of DHEA hormone leads to dirturbances on  circulating cortisol/DHEA ratio (3-3.5 AU SEV vs 1-1.2 AU CT). We also observed by in vitro Transwell migration, an enhance on migratory response over fibronectin (9.5x104 cells ± 4 SEV vs 3.8x104 cells ± 6 CT), CXCL12 (12.6x104 cells ± 5 SEV vs 1.8x104 cells ± 5 CT), fibronectin + CXCL12 (13x104 cells ± 9 SEV vs 2.9x104  mean ± 4 CT) and fibronectin + TNF-α (25x104 cells ± 7 SEV vs 9.3x104 cells ± 4 CT) as well as with Cortisol and DHEA pre- treatment in different concentrations (preliminary results).  Conclusion: These results indicate that endocrine disturbances, correlated to a systemic inflammatory profile, may also contribute to enhance migratory potential of T lymphocytes to inflammatory sites, including the heart tissue, being thus involved in the cardiopathy seen in this disease.