Immunomodulatory activity of dehydroepiandrosterone and oxygenated and fluorinated androstenes.

MARIA BELEN VECCHIONE; JAVIER EIRAS; FLAVIA MICHELINI; LAURA ALCHÉ; MARIA FLORENCIA QUIROGA; ANDREA BRUTTOMESSO; LYDIA GALAGOVSKY

San Fransisco

Congreso; 248 th ACS National Meeting; 2014

The results of nearly 50 years of research have shown that DHEA (dehydroepiandrosterone) is a multi-functional steroid implicated in a broad range of biological processes. DHEA, an androstene hormone, has been shown to possess a wide range of beneficial biological effects mainly attributed to immune system modulation. DHEA is metabolized into more active metabolites, that is, AED and AET, as well as testosterone and estradiol. AED and AET have been reported to prevent infections and counteract the immune suppressive action of hydrocortisone, thus leading to beneficial effects in diverse human diseases. In this work we report the syntheses of AED, AET and six androstenes oxygen- and fluorinated in C-3 and C-7 derived from DHEA. The immune regulation of DHEA and its related compounds were evaluated. The cytotoxic concentration, the modulation on TNF-α and IL-6 production by macrophages were determined for each compound. The antiagiogenic activity was also studied by the effect in VEGF expression and in the migration of HUVEC cells. Finally, the major histocompatibility complex (class I and II) expression and the IL-12 production were measured in dendritic cells stimulated with M. tuberculosis. The results showed that AED, AET and any of the synthetic compounds with less androgenic effect, can be relevant in immunomodulatory therapies.