ADRENAL STEROIDS MODULATE THE IMMUNE RESPONSE DURING BRUCELLA ABORTUS INFECTION

GENTILINI M. VIRGINIA; VELAZQUEZ LIS; BARRIONUEVO PAULA; ARRIOLA BENITEZ PAULA C.; GIAMBARTOLOMEI GUILLERMO H.; DELPINO M. VICTORIA

Congreso; LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

Brucella abortus (Ba) induces an inflammatory response thatcould stimulate the endocrine system resulting in the secretion ofglucocorticoids and dehydroepiandrosterone (DHEA). Our aim wasto evaluate the role of adrenal hormones on the immune responsein brucellosis. We found an increased in the cortisol/DHEA ratio insera from brucellosis patients (p<0,05) (electroquimioluminisence).Since monocytes are the replication niche of Ba, we evaluatedthe role of adrenal hormones on IL-1β, IL-6, TNF-α, MCP-1, IL-8production (ELISA), MMP-9 activity (zymography) and MHC-I,MHC-II, CD40, CD86 and CD54 expression (flow cytometry) inhuman monocytes (THP-1) in the presence of cortisol or DHEA.Our results showed that DHEA induced the secretion of cytokines,MMP-9 production and the surface expression of MHC-I and MHCIIand co-stimulatory molecules in Ba infected THP-1 cells. Cortisoltreatment inhibited the expression of these molecules during Bainfection. When experiments were performed in the presence ofboth cortisol and DHEA, we observed a significant increase inthe expression of all molecules studied respect to Ba-infecteduntreated cells or Ba-infected cells treated with cortisol. Theseresults indicated that DHEA was able to reverse the inhibitoryeffect induced by cortisol. It has been described that Ba can surviveinside macrophages and this phenomenon could be explainedat least in part by the inhibition of MHC-I and MHC-II expressioninduced by IFN-γ. Our results indicated that treatment with DHEAresulted in significant recovery of the inhibition of IFN-γ-inducedMHC-I (p<0,05) and MHC-II (p<0.01) expression mediated by Bainfection. Cortisol had no effect on the down-modulation of IFN-γ-induced MHC-I and MHC-II expression mediated by Ba. When bothhormones were administered together the effect was the sameas with DHEA alone. This work is the first report demonstratingthe influence of the endocrine system on the immune responsein Brucellosis.