immunology of infectious and parasitic diseases - XXXVII Congress ...

IMMUNOENDOCRINE INTERACTIONS DURING LYMPHOCYTE MIGRATION
IN HUMAN CHAGAS DISEASE
LUIZ RICARDO BERBERT (1) ; ANA ROSA PÉREZ (2) ; ROMINA MANARIN (2) ;
FLORENCIA GONZALEZ (2) ; JACKELINE PETRUCCI (2) ; JUAN BELOSCAR (2) ;
OSCAR BOTTASSO (2) ; WILSON SAVINO (1)
(1) Laboratory on Thymus Research - Oswaldo Cruz Institute – Brazil;
(2) Immunology Institute – Rosario National University – Argentina.
Introduction: 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
(9.5x10 4 cells ± 4 SEV vs 3.8x10 4 cells ± 6 CT), CXCL12 (12.6x10 4 cells ± 5
SEV vs 1.8x10 4 cells ± 5 CT), fibronectin + CXCL12 (13x10 4 cells ± 9 SEV vs
2.9x10 4 mean ± 4 CT) and fibronectin + TNF-α (25x10 4 cells ± 7 SEV vs
9.3x10 4 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.