Effects of adrenal steroids on the mycobacterial-driven-IFN-gamma production by peripheral blood mononuclear cells from tuberculosis (TB) patients and their household contacts

BOZZA, VERóNICA; D'ATTILIO, LUCIANO; DíDOLI, GRISELDA; SANTUCCI, NATALIA; NANNINI, LUIS; DEL REY, ADRIANA; BESEDOVSKY, HUGO; BAY, MARíA LUISA

Río de Janeiro

Congreso; 7th International Society for NeuroImmuno Modulation Congress; 2008

Earlier studies in TB patients revealed imbalanced immune-endocrine responses with adrenal steroids (cortisol and DHEA) modifying their specific cell-mediated immune response (CMI). Household contacts (HHC) of contagious TB patients have an increased risk of developing the disease, but most of them develop a sub-clinical and self-controlled process. HHC and TB patients share environmental and socioeconomic conditions, amenable for analyzing their CMI to mycobacteria, like potential differences in adrenal-steroid-induced modifications. To this end, 19 HHC, 38 untreated TB patients and 18 healthy controls (Co), of similar age, were studied. Stimulation of peripheral blood mononuclear cells (PBMC) with M. tuberculosis sonicate revealed no differences in the in vitro lymphoproliferation seen in HHC and Co, but both groups had a higher response than patients with severe TB (n=9, p<0.01). Higher amounts of  IFN-ã were seen in culture supernatants from stimulated PBMCs of HHC, significantly different from values recorded in Co and TB patient counterparts (p<0.01 and p<0.04, respectively). Further in vitro studies by adding both steroids (cortisol 10-6µM and DHEA: 10-7, 10-8, 10-9 µM) showed that cortisol recurrently inhibited mycobacterial antigen-driven IFN-g production (60-70 %) in all study groups, regardless of the presence of DHEA, but less pronounced in HHC. HHC can develop a preserved CMI, in terms of IFN-g production, even when undergoing an in vitro reproducible stressful-induced condition, like cortisol exposure