Adrenal steroids modulate the immune response during Brucella abortus infection

GENTILINI M. V., VELÁSQUEZ L. N., BARRIONUEVO P., ARRIOLA BENITEZ P. C., GIAMBARTOLOMEI G. H., DELPINO M. V

Congreso; LXII Reunión Científica de la Sociedad Argentina de Inmunología; 2014

Brucella abortus (Ba) induces an inflammatory response that could stimulate the endocrine system resulting in the secretion of glucocorticoids and dehydroepiandrosterone (DHEA). Our aim was to evaluate the role of adrenal hormones on the immune response in brucellosis. We found an increased in the cortisol/DHEA ratio in sera from brucellosis patients (p<0.05) (electroquimioluminisence). Since monocytes are the replication niche of Ba, we evaluated the role of adrenal hormones on IL-1β, IL-6, TNF-α, MCP-1, IL-8 production (ELISA), MMP-9 activity (zymography) and MHC-I, MHC-II, CD40, CD86 and CD54 expression (flow cytometry) in human 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 MHC-II and co-stimulatory molecules in Ba infected THP-1 cells. Cortisol treatment inhibited the expression of these molecules during Ba infection. When experiments were performed in the presence of both cortisol and DHEA, we observed a significant increase in the expression of all molecules studied respect to Ba-infected untreated cells or Ba-infected cells treated with cortisol. These results indicated that DHEA was able to reverse the inhibitory effect induced by cortisol. It has been described that Ba can survive inside macrophages and this phenomenon could be explained at least in part by the inhibition of MHC-I and MHC-II expression induced by IFN-γ. Our results indicated that treatment with DHEA resulted in significant recovery of the inhibition of IFN-γ-induced MHC-I (p<0.05) and MHC-II (p<0.01) expression mediated by Ba infection. Cortisol had no effect on the down-modulation of IFN-γ-induced MHC-I and MHC-II expression mediated by Ba. When both hormones were administered together the effect was the same as with DHEA alone. This work is the first report demonstrating the influence of the endocrine system on the immune response in Brucellosis.