New insights into how dexamethasone could aid TB treatment
Tuberculosis (TB) remains a global health challenge, affecting more than 10 million people annually and causing around 1.25 million deaths each year. Amid ongoing efforts to curb TB, researchers at Trinity College Dublin, based at St James’s Hospital in Dublin, are revisiting the role of steroids as part of host-directed therapy. Their recent work, published in Scientific Reports, suggests that dexamethasone—a potent glucocorticoid—may enhance the lungs’ innate immune response while simultaneously reducing inflammatory damage during TB infection.
What the study set out to learn
Glucocorticoids, including dexamethasone, are already used in specific TB cases such as TB meningitis. Yet, scientists have long debated their net effect on the immune system, particularly on macrophages—the frontline cells that engulf and attempt to destroy Mycobacterium tuberculosis (Mtb). The Trinity College Dublin team sought to determine how dexamethasone influences macrophage function and whether it could serve as a universal adjunct to antimicrobials in TB care.
How the experiments were conducted
Researchers studied macrophages derived from healthy volunteers’ blood and from lung fluid donated by patients undergoing routine bronchoscopies. These cells were treated and infected with Mtb in laboratory conditions. By observing the infected macrophages, scientists evaluated how dexamethasone affected the cells’ energy metabolism, inflammatory signaling, and capacity to control the mycobacterial infection.
Key findings and their meaning
1) Metabolic shift in macrophages: Dexamethasone reduces glycolysis in both lung- and blood-derived macrophages, lowering the energy available to the cells. This metabolic change appears to influence how macrophages respond to TB infection.
2) Inflammation control: The drug dampens production of several cytokines, including IL-1β, TNF, IL-6, IL-8 and IL-10. While excessive inflammation can damage lung tissue, a balanced response is essential to fighting infection.
3) Enhanced antimicrobial activity: Despite reduced inflammation, dexamethasone-treated macrophages showed decreased bacterial burden. The team traced part of this effect to autophagy and phagosomal acidification—processes by which macrophages degrade and clear bacteria.
4) macrophage origin matters: Macrophages from different tissues responded differently to glucocorticoids, underscoring that tissue origin can influence drug effects. This insight is important for designing targeted therapies that optimize antimicrobial defense while controlling inflammation.
Overall, the study provides one of the first demonstrations that dexamethasone can temper harmful inflammation without compromising, and may even enhance, the macrophage’s ability to clear Mtb in primary human lung macrophages.
Implications for patients and future therapy
The findings offer a potential rationale for using steroids as an adjunctive therapy alongside antimicrobials in TB treatment, particularly where inflammation is excessive. Beyond active TB, dexamethasone could have a role in preventive therapy to reduce progression from latent infection to active disease by supporting macrophage function while controlling inflammation.
Experts caution that more research is needed before changing clinical practice. The ultimate goal is to develop targeted steroid therapies—potentially delivered to the lungs via inhaled nanoparticles—to maximize macrophage antimicrobial activity while minimizing systemic side effects. The team also aims to map how steroids alter metabolic pathways in lung versus blood-derived macrophages, guiding smarter, organ-specific treatments.
Quotes from the researchers
“Our study shows that dexamethasone, known for dampening inflammation, can also help macrophages fight tuberculosis more effectively,” said a senior researcher from Trinity College Dublin. “This challenges the assumption that steroids always suppress immunity and opens the door to smarter, targeted adjunctive therapies that balance inflammation control with antimicrobial defense.”
“Steroids are among the most under-used adjunctive therapies for TB in clinical practice,” noted another clinician-researcher. “Dexa can temper inflammation while supporting the macrophage’s ability to control infection, offering a path to redefine steroid use in TB care.”
Looking ahead
Continued work will explore lung-specific delivery methods and identify metabolic pathways uniquely affected in lung macrophages. If successful, these advances could translate into more effective TB therapies that combine antimicrobial action with precise immune modulation, potentially shortening recovery times and reducing long-term damage for patients.
