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

QUATTONI IA; DA SILVA OLIVEIRA BARBOSA; ROGGERO E; GONZALEZ F; FERNANDEZ R; BOTTASSO O; PEREZ A; VILLAR S

Tucumán

Congreso; LXVII Reunión Científica de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Glucocorticoids (GC) are essential to control inflammation. Previously, we demonstrated that Trypanosoma cruzi-infected mice present an activation of the hypothalamus-pituitary-adrenal axis in response to increased systemic amounts of IL-1β, TNF-α and IL-6. In addition, we described the existence of two phases involved in GC synthesis during acute infection, wherein the 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 findings suggested that other stimuli are operating at adrenal level to preserve such increased GC synthesis. Since Prostaglandin-E2 (PGE2) is known to stimulate adrenal steroidogenesis via the local cAMP supply, we have now evaluated the expression of PGE2-synthase as a surrogate of intra-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 beassociated with a biphasic action of PGE2, probably favored by intra-adrenal production of proinflammatory cytokines.