Effect of DHEA in Diabetes type 2 & Tuberculosis Comorbidity

LOPEZ TORRES, MANUEL O.; MAEQUINA CASTILLO, BRENDA; MATA ESPINOSA, DULCE; BARRIOS PAYAN, JORGE A; CARRANZA, ANDREA; HERNANDEZ PANDO, ROGELIO

Cancun

Congreso; XII Congress of the Latin American Association of Immunology & XXIII Congress of the Mexican Society of Immunology; 2018

Latin American Association of Immunology (ALAI) and the Mexican Society of Immunology (SMI)

In the last three decades, 314 million new cases of Diabetes Mellitus (DM) were reported. This pandemic disease is a well-recognized risk factor for Tuberculosis (TB) with a 3-fold susceptibility rate increase. Although studies have found several relations between TB and DM, the specific mechanisms and factors that make diabetic patients more susceptible to developing TB are not yet fully understood. Both diseases are characterized by excessive glucocorticoid production and the overstimulation of 11-β-hydroxysteroid dehydrogenase type 1 (11-βHSD1). This enzyme has reductase activity for 11-ketosteroids products and favors their conversion to cortisol. Steroid hormones, such as dehidroepiandrosterone (DHEA) or its synthetic analog 16-alpha-bromoepiandrosterone (HE2000), which is a modified androstane adrenal hormone without androgenic effects, display immune restoration activity in several infectious and metabolic diseases. Thus, hypercortisolism and decreased DHEA production could contribute to immune suppression in TB-DM individuals. Therefore, we assessed the effect of HE2000 in TB progression in the presence of DM2 in an experimental murine model. Our results showed that HE2000 diminished bacterial load in lungs in comparison with vehicle control. However, the half-life of the animals was reduced. These results suggest that steroids play a key role in downregulating the immune response and their modulation during comorbid diabetes contributes a reduced immune response that is less effective in controlling bacterial replication within the lungs. The results suggest that HE200 is a potential candidate as an immune adjuvant with standard antibiotic therapy in the disease.