Study of 7-oxo-dehydroepiandrosterone as potencial adjuvant for the treatment of pulmonary tuberculosis.

DULCE MATA; RICARDO MÁRQUEZ VELASCO; MARÍA BELÉN VECCHIONE; MARIA FLORENCIA QUIROGA; CLAUDIA DEL CARMEN MELUCCI GANZARAIN; JORGE BARRIOS PAYÁN; BRENDA MARQUINA; ANDREA BRUTTOMESSO; ROGELIO HERNANDEZ PANDO

Ciudad Autonoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2017

Tuberculosis (TB) affects one-third of the world´s population but BCG vaccine, the prophylactic available against Mycobacterium tuberculosis(Mtb), does not prevent pulmonary TB in adults. Understanding the immunopathogenesis of TB would facilitate the choice of newimmunotherapeutic agents. We focus on the role of DHEA and its metabolite 7-oxo-DHEA in the context of HIV-TB coinfection. We reportedHIV-TB patients exhibited high plasma levels of these hormones and that 7-oxo-DHEA positively correlated with absolute CD4+ T cell count,CD4+ T cell nadir values and with TB restricted to the lungs. Additionally, 7-oxo-DHEA increased lymphocyte proliferation and the production ofIFN-G of peripheral blood mononuclear cells from coinfected individuals.We aimed to study the use of 7-oxo-DHEA as a modulator of Mtb-specific immune responses. Human THP-1 and alveolar murine MH-Smacrophage cell lines were infected with Mtb H37Rv in presence of DHEA or 7-oxo-DHEA. Macrophages were stained to measure Mtbphagocytosis and were lysed to quantify colony forming units (CFU) as a measure of mycobacterial growth. Additionally, male BALB/c micewere infected and treated with 7-oxo-DHEA (15, 50 or 200 Ug/day, 3 times a week) by subcutaneous and intratracheal administration. Animalswere killed at 90 days post-infection. Lungs and spleen from each mouse were used for counting CFU.