Targeted Steroid Use in Tuberculosis: A New Complement to Antimicrobial Therapy
Tuberculosis (TB) remains a global health challenge, affecting more than 10 million people each year. A new study published in Scientific Reports explores how a targeted steroid approach could enhance immune defense while curbing damaging inflammation. The findings point to a nuanced role for steroids like dexamethasone in TB care, one that goes beyond simply dampening inflammation.
How steroids impact macrophages and the TB battle
Macrophages are frontline immune cells that engulf and attempt to destroy Mycobacterium tuberculosis (Mtb), the bacterium that causes TB. The study examined macrophages derived from healthy volunteers and from lung fluid donated by patients undergoing routine bronchoscopies, then exposed these cells to Mtb in a controlled lab setting. When dexamethasone was introduced, several important effects emerged.
First, dexamethasone reduced glycolysis—the primary energy source for many cells. By limiting this energy supply, the drug subtly reprograms cellular metabolism in ways that can influence how macrophages respond to infection.
Second, the steroid tempered the production of inflammatory cytokines. While controlled inflammation is essential to fight infection, excessive inflammation can cause tissue damage and worsen outcomes in TB. The study suggests that dexamethasone can reduce inflammatory damage without completely suppressing the macrophages’ antimicrobial functions.
Crucially, the research found that infected macrophages treated with dexamethasone showed increased survival, indicating that the cells may be better able to withstand the deleterious effects of TB and the immune response. At the same time, bacterial burden within these cells was reduced, a sign that the immune system retained its capacity to kill or clear bacteria even under steroid influence.
Mechanisms: autophagy and phagosomal acidification
The team identified key mechanisms by which dexamethasone enhances bacterial clearance. Autophagy—a process by which cells degrade and recycle their own components—appears to be promoted in the presence of the steroid. Phagosomal acidification, the acid-based breakdown within phagosomes that helps destroy engulfed bacteria, also contributes to the reduced bacterial burden. Together, these processes suggest that dexamethasone can support the macrophage’s antimicrobial arsenal rather than merely suppress it.
Clinical implications: redefining steroid use in TB care
Historically, steroids have been used as adjunctive therapy in select TB conditions, such as TB meningitis, where inflammation can be life-threatening. However, their broader role in pulmonary TB and other forms has been less clear. Prof. Joseph Keane of Trinity College Dublin highlighted a practical dilemma: steroids are underused in TB care despite their potential to modulate harmful inflammation while maintaining antimicrobial defense.
The new findings offer a more nuanced view: dexamethasone may calm excessive inflammation without eroding the immune system’s ability to combat Mtb. This balance could help patients with severe TB forms or excessive inflammatory responses, potentially improving outcomes when used alongside standard antimicrobial therapies.
What comes next?
While the study provides compelling laboratory evidence, translating these results into routine clinical practice will require carefully designed clinical trials. Questions remain about dosing, timing, patient selection, and how dexamethasone interacts with different TB drugs and patient comorbidities. Researchers emphasize that any broader adoption must carefully weigh benefits against risks such as immunosuppression, metabolic effects, and potential side effects of steroids.
Bottom line
The research supports a targeted, adjunctive role for steroids in TB care—one that augments macrophage antimicrobial activity while curbing damaging inflammation. If clinical trials confirm these lab-based insights, dexamethasone could become a more precisely used tool in the TB treatment toolkit, complementing antibiotics rather than simply dampening immune responses.
