GLUCOCORTICOIDS AND IMMUNE-ENDOCRINE DYSREGULATION IN TUBERCULOSIS AND TYPE 2 DIABETES COMORBILITY.

DIAZ ARIANA; BÉRTOLA DIEGO; BERTOLIN YESICA; BAY MARÍA LUISA; D'ATTILIO LUCIANO; GALLUCCI GEORGINA; LIOI SUSANA; BOTTASSO OSCAR; FERNANDEZ ROCIO DEL VALLE; BONGIOVANNI BETTINA; GARDEÑEZ WALTER; GALLIANO ROMINA

Tucumán

Congreso; Congreso LXVII de SAI; 2019

SAI

Pulmonary tuberculosis (TB) is a major health problem worldwide, aggravated by the convergence of type 2 diabetes mellitus (DM). This comorbidity also constitutes a natural model for studying immune-endocrine-metabolic disturbances certainly implicated in disease pathogenesis. In previous studies we observed that TB patients displayed increased plasma amounts of cortisol and proinflammatory mediators. However, TB+DM patients showed even higher levels of IFN-γ (vs TB), IL-6, C reactive protein and cortisol (vs. DM), with equally augmented values of IL-10 in TB groups. Unlike peripheral blood mononuclear cells (PBMC) from TB cases showing a decreased glucocorticoid -GC- receptor isoforms ratio (GRα/GRβ), TB+DM patients had a normal balance in this regard (appropriate for GC signaling), along with an increased expression of 11βHSD1, enzyme facilitating cortisone-cortisol conversion. The particular scenario of TB+DM patients (hyperglycemic environment plus increased cortisolemia) induced us to assess immune response against Mycobacterium tuberculosis (Mtb) exposing PBMC to stress-related cortisol concentrations and supraphysiological doses of glucose (10, 20 and 40 mM). Compared to their TB (n=7), DM (n=9) and HCo (n=7) counterparts, the PBMC of patients with TB+DM (n=6) had the highest blastogenic response with a marked Th1 bias (increased IL-2 vs TB, DM & HCo, p