Overview: Rethinking Steroids in TB care
Tuberculosis (TB) remains a global health challenge, infecting more than 10 million people annually and claiming around 1.25 million lives each year. While corticosteroids like dexamethasone are used in select TB scenarios, notably TB meningitis, their broader impact on immune cells—especially lung macrophages—has been unclear. A new study from Trinity College Dublin, based at St James’s Hospital, Dublin, investigates whether dexamethasone can influence macrophages to better kill the TB-causing bacteria while reducing inflammatory damage. Published in Scientific Reports, the work explores host-directed therapy strategies that could complement standard antimicrobials.
Study design: How researchers approached the question
The team examined macrophages derived from healthy volunteers’ blood and macrophages obtained from lung fluid donated during routine bronchoscopies. Researchers infected these macrophages with Mycobacterium tuberculosis (Mtb) in the lab and then treated them with dexamethasone to observe changes in immune function. The goal was to understand whether this glucocorticoid shapes the macrophages’ ability to control infection without amplifying harmful inflammation.
Key findings: Dexa dampens inflammation but preserves antimicrobial power
Several important observations emerged from the experiments. First, dexamethasone reduced glycolysis in both lung- and blood-derived macrophages, lowering the energy available to the cells. Second, it decreased the production of several inflammatory cytokines, including IL-1β, TNF, IL-6, IL-8, and IL-10. While dampening excessive inflammation can prevent tissue damage, some cytokines also play roles in fighting infection, so this balance is critical.
Interestingly, Mtb-infected macrophages exposed to dexamethasone showed greater bacterial survival, suggesting a protective effect for host cells against infection-induced cell death. Yet the same treatment reduced the overall bacterial burden within these cells. The researchers linked this improvement to enhanced autophagy and phagosomal acidification—cellular processes that promote the degradation and clearance of bacteria. In short, dexamethasone appeared to bolster antimicrobial defense while tempering inflammation.
Tissue origin matters: personalized responses to steroids
The study highlighted that macrophages from different tissue sources did not respond identically to glucocorticoids. This finding hints that tissue origin can influence how macrophages react to steroids, informing strategies to tailor host-directed therapies for TB. It also marks one of the first studies to show that dexamethasone can curb inflammation without compromising, and may even support, antimicrobial activity in primary human lung macrophages infected with Mtb.
Implications for patient care and future directions
These results bolster the rationale for using steroids as adjunctive therapy alongside antimicrobials in TB, particularly where inflammation is excessive. Steroids could also play a role in TB preventive therapy to reduce the risk of progression from latent infection to active disease. The researchers envision developing macrophage-targeted steroid approaches—potentially delivered via inhaled nanoparticles—that concentrate the drug’s effects in lung tissue while minimizing systemic side effects.
Dr. Donal Cox, a senior research fellow at Trinity College Dublin, notes that dexamethasone’s anti-inflammatory actions may also enhance the macrophage’s capacity to combat TB. Prof. Joseph Keane adds that steroids are among the most under-used adjunctive tools in TB care and may help redefine how we balance inflammation control with antimicrobial defense. The team plans to explore how steroids alter distinct metabolic pathways in lung versus blood-derived macrophages to guide next-generation therapies.
What comes next for TB management?
While this study does not suggest steroids replace antimicrobials, it points toward smarter, targeted adjunctive therapies that could improve patient recovery by reducing debilitating inflammation and accelerating bacterial clearance. Realizing this potential will require further research, including clinical trials and development of targeted delivery methods for the lungs.
