Evidence that normal to high glucose supplementation modifies the inhibitory effect of cortisol on the in vitro anti-TB response

FERNANDEZ R; DIAZ A; BONGIOVANNI B; BERTOLA D; GARDEÑEZ W; PENT MARIA VICTORIA; BAY ML; BOTTASSO O; DATTILIO L

Cancún

Congreso; Congress of the Latinamerican association of Immunology; 2018

ALAI

(TB) is a major health problem worldwide and the leading cause of death by an infectious agent, Mycobacterium tuberculosis (Mtb). In 2016, WHO reported 10.4million new TB cases [1], 15% of them attributed to co-morbidity TB plus type 2 diabetes mellitus (T2DM)[2]. In fact, T2DM may increase more than 3 times the possibility of developing active TB, which otherwise develop in 5?10% of Mtb-infected individuals (one third of the world population). Our previous results in patients with pulmonary TB and T2DM (TB+T2DM) showed a more pronounced adverse immune-endocrine profile than those with TB alone; for instance, much higher levels of IFN-γ, IL-6 and cortisol. Infectious processes are a source of host stress leading to the activation of the hypothalamic-pituitary-adrenal axis (HPA) which increases cortisol production. Besides its metabolic functions, cortisol acts as an extrinsic regulator of the immune response (IR) inhibiting, at high concentrations, the proinflammatory response as well as the specific cellular IR against Mtb[4]. As such, we analysed whether high doses of cortisol(mirroring a stress situation) modified the Mtb-induced response of blood mononuclear cells (PBMC) of patients with TB+T2DM when compared to the ones yielded by TB cases, patients with T2DM (T2DM) and healthy subjects (HCo), in presence of physiological and supraphysiological glucose concentrations, or not.Subjects (age range 18?70 years), which were all HIV negative and recruited after signing the written informed consent, were distributed as follows: TB+T2DM (n=10), TB (n=36), T2DM (n=13) and HCo (n=40). Each participant was evaluated for the routine laboratory assays along with the circulating levels of steroid hormones, and the Mtb-driven lymphoproliferative capacity of the PBMC [Mtb strain H37rv killed by γ radiation (Mtbi)]. While the three patient groups had a significant increase in the number of leukocytes (p