Human chronic Chagas cardiomyopathy is associated to a disrupted activation of the hypothalamus-pituitary-adrenal axis and a systemic inflammatory state

GONZÁLEZ, FLORENCIA B.;.; PACINI, ANTONELLA; ; VILLAR, SILVINA;; LEIVA, RODOLFO; ; BOTTASSO, OSCAR; ; PÉREZ,ANA ROSA

Otro; 1st European Psychoneuroimmunology Network (EPN) Autumn School: Lung- Brain Axis in Health and Disease; 2022

Chronic Chagas cardiomyopathy (CCC) is a disease caused by Trypanosoma cruzi. CCC pathogenesis is not completelyunderstood, but the balance between host immune response and parasite persistence seems crucial for its establishmentand progression. Accordingly, we investigated the immuno-endocrine response in chagasic patients and their possibleinfluence on CCC pathogenesis. CCC patients and T. cruzi-seronegative individuals were recruited. The concentration ofcortisol, DHEA-S, TNF-alpha, IL-6, and adipocytokines was determined in serum. The expression of glucocorticoid receptors(GR-alpha is the functional receptor while GR-beta acts as an inhibitor of GR-alpha), 11beta-HSD1 (which regulates cortisolbioavailability) and genes regulated by cortisol and involved in the inflammatory response (IL-6, IFN-gamma, IL-1beta, andtristetraprolin) was evaluated by RT-qPCR in peripheral blood mononuclear cells (PBMCs). A systemic inflammatory statewas evident (as judged by IL-6 and leptin levels) in CCC individuals paralleled by a disrupted activation of the hypothalamuspituitary-adrenal axis, characterized by decreased DHEA-S and cortisol levels together with an unbalanced cortisol/DHEA-Sratio. RG-alpha expression in CCC patients did not differ from the control group, 11beta-HSD1 expression was increased inpatients, and RG-beta expression was not detectable. mRNA levels of IL-6, IFN-gamma, and IL-1beta tended to increase inthe CCC group, in presence of decreased tristetraprolin transcripts. Both tristetraprolin/IFN-gamma and tristetraprolin/IL-1beta ratios were decreased in CCC patients. The present results do not indicate a mechanism of cortisol resistance in PBMCsfrom CCC patients, but the adverse systemic endocrine milieu observed may favor the establishment of animmunometabolic pro-inflammatory state that promotes further myocardial tissue damage.