BIPHASIC EFFECT OF PROSTAGLANDINS AS EVIDENCE OF AN ALTERNATIVE GLUCOCORTICOID SYNTHESIS PATHWAY DURING ACUTE EXPERIMENTAL CHAGAS DISEASE.

QUATTONI IA; GONZÁLEZ F ; PEREZ AR; DA SILVA OLIVEIRA BARBOSA E; FERNÁNDEZ RV ; VILLAR SR; ROGGERO E ; BOTTASSO O

Tucuman

Congreso; LXVII Reunion Anual de la SAI; 2019

Sociedad Argentina de Inmunologia

Glucocorticoids (GC) are essential to control inflammation. Previously, we demonstrated thatTrypanosoma cruzi-infected mice present an activation of the hypothalamus-pituitary-adrenalaxis in response to increased systemic amounts of IL-1β, TNF-α and IL-6. In addition, wedescribed the existence of two phases involved in GC synthesis during acute infection, whereinthe remarkably increased GC levels seen after 14 days post-infection (dpi) were dissociatedfrom ACTH concentrations lowering to basal levels by that time-point evaluation. These findingssuggested that other stimuli are operating at adrenal level to preserve such increased GCsynthesis. Since Prostaglandin-E2 (PGE2) is known to stimulate adrenal steroidogenesis via thelocal cAMP supply, we have now evaluated the expression of PGE2-synthase as a surrogate ofintra-adrenal production of PGE2, at different dpi (real time PCR and western blot). In parallel,we assessed PKA-p/PKA ratio as a measure of the ACTH-dependent pathway activation(western blot) and the intra-adrenal cytokine production (IL-1β and IL-6, real time PCR).C57BL/6 mice were infected with T. cruzi or inoculated with saline. Blood and adrenals were obtained every 2-3 days along infection. Measurements of PGE2-S mRNA and its protein amounts showed two expression peaks. The first one coincided with the maximum release of ACTH hormone, while the second one paralleled the ACTH-independent phase. Proinflammatory intra-adrenal cytokine levels were augmented throughout infection.Collectively, these data suggest that GC production during T. cruzi acute infection seems to be associated with a biphasic action of PGE2, probably favored by intra-adrenal production of proinflammatorycytokines.