Therapeutic potential of 7-oxo-DHEA as an adjunctive host-directed therapy for pulmonary tuberculosis

Although anti-tuberculous therapy effectively eradicates Mycobacterium tuberculosis (Mtb) infection, it requires prolonged treatment with multiple drugs, often resulting in adverse effects and poor compliance. Therefore, novel immunotherapeutic strategies are needed to enhance host defense and improve disease management. In this study, we investigated the immunomodulatory and antimicrobial properties of 7-oxo-dehydroepiandrosterone (7-oxo-DHEA, 7-OD), a derivative of the endogenous hormone DHEA, using both in vitro and in vivo models of Mtb infection. In culture, 7-OD exerted a bacteriostatic effect on Mtb growth. In macrophage infection assays, it enhanced intracellular bacterial clearance and modulated cytokine secretion, favoring a pro-inflammatory profile. Notably, in a murine model of progressive pulmonary tuberculosis, 7-OD treatment significantly reduced bacterial burden and mitigated lung pathology. These findings indicate that 7-OD enhances host immune responses to control Mtb infection and limit tissue damage. Further studies are warranted to evaluate its applicability as an adjunctive host-directed therapy in combination with standard anti-TB drugs.