ANTI-INFLAMMATORY EFECT OF RIFAMPICIN AND DEHYDROEPIANDROSTERONE ON A MACROPHAGIC HUMAN CELL LINE

DIAZ, ARIANA; BONGIOVANNI, BETTINA; MASSA, ESTEFANIA; GALLUCCI, GEORGINA; HARTE, LUCIA; DI DOMENICO, MARCOS; DIAB, MAGDALENA; DERIO, MARISA; D ATTILIO, LUCIANO; BAY, MARÍA LUISA

Congreso; Annual Meeting of Bioscience Societies 2021; 2021

Tuberculosis (TB) is a major health problem worldwide. The etiologic agent, Mycobacterium tuberculosis (Mtb) is transmitted by air and captured by lung macrophages (Mf). Mf activation along with an efficient cellular immune response is required for Mtb elimination, which at the same time can mediate tissue damage. We previously found that TB patients at the time of diagnosis showed an immune-endocrine imbalance: high plasma levels of pro- and anti-inflammatory mediators and cortisol, as well as lowered Dehydroepiandrosterone (DHEA) levels. During the specific anti-TB treatment, the proinflammatory mediators and DHEA levels reach values like those found in healthy controls. Rifampicin (R) is a potent antimicrobial agent and a major drug in TB treatment, its antibacterial activity is mediated by the inhibition of bacterial RNA polymerase. There is evidence that R also modulates the host immune response, influencing lymphocyte migration, cytokine production and phagocytosis. In a previous study on a Mf cell line, DHEA treatment decreased the colony-forming units of Mtb even in the presence of stressful and physiological doses of cortisol. Given this background, we now investigated whether R, with or without DHEA, could affect the functional capacity of Mf (adherent human THP-1 cells, activated with 30 ng/ml of phorbol-12-myristate-13-acetate -PMA- for 24hs). TB patients under treatment show R plasma levels between 8–24 µg/ml. In a dose response study (5, 10, 15, 20, 25 µg/ml) the 15 µg/ml dose was selected. When Mf were treated with R or DHEA (10-6M, 10-7M, 10-8M), there were no differences in supernatants levels of the pro-inflammatory cytokine IL-1β (n=5, for each treatment). However, the addition of R+DHEA significantly decreased IL-1β production regarding Mf untreated cultures (p