A new study reveals that the targeted use of a common steroid could offer a powerful complementary treatment for tuberculosis, a disease that affects over 10 million people worldwide each year. Researchers have found that the steroid dexamethasone can enhance the ability of the body’s own immune cells to kill the bacteria that cause tuberculosis while simultaneously reducing the excessive inflammation that leads to severe lung damage. This dual action offers a promising strategy to improve outcomes for patients undergoing long and often difficult antibiotic regimens.
The findings, published in Scientific Reports, provide critical evidence that could reshape how clinicians use steroids in tuberculosis care. While corticosteroids are already administered in some severe cases, such as tuberculous meningitis, their broader application has been limited by an incomplete understanding of their effects on the immune system during infection. This research clarifies that dexamethasone does not compromise the immune system’s antimicrobial defenses; instead, it appears to bolster them by targeting specific cellular pathways. By modulating the host’s immune response, this approach, known as host-directed therapy, opens a new front in the battle against a persistent and increasingly drug-resistant global health threat.
Balancing Immune Response and Damage
The primary challenge in treating tuberculosis is not just eliminating the bacterium, Mycobacterium tuberculosis (Mtb), but also managing the body’s reaction to it. The host immune response is a double-edged sword; while it is essential for containing the infection, a dysregulated or excessive inflammatory response is the principal cause of the debilitating lung damage seen in the disease. When Mtb infects the lungs, the immune system walls off the bacteria within structures called granulomas. In many cases, this leads to a state of latent infection where the bacteria are contained and the person shows no symptoms.
However, in active TB, this inflammatory process can become destructive. The chronic inflammation can lead to caseous necrosis, a process where lung tissue is destroyed, forming cavities. This damage is often permanent, and many survivors of TB are left with long-term respiratory impairment and a reduced quality of life, even after the infection has been cured with antibiotics. The new study demonstrated that dexamethasone helps temper this damaging inflammation by reducing the production of both pro- and anti-inflammatory signaling molecules, known as cytokines, in the immune cells. This suggests the steroid could help preserve lung function by preventing the immune system from causing excessive collateral damage during the infection.
Enhancing the Body’s Cellular Defenders
The research focused on macrophages, the primary immune cells that Mtb infects and uses as a niche to replicate. These cells are the first line of defense, engulfing invading bacteria in an attempt to destroy them. However, Mtb has evolved sophisticated mechanisms to survive inside macrophages, effectively turning its predator into a long-term host. The study, conducted by researchers at Trinity College Dublin, investigated how dexamethasone affects the function of these crucial cells.
Scientists studied macrophages isolated from the blood of healthy volunteers and from lung fluid donated by patients. In the laboratory, they infected these cells with Mtb and treated them with dexamethasone. The results showed that the steroid-treated macrophages were better at killing the bacteria. This enhanced bacterial clearance is achieved through several mechanisms, including autophagy—the cell’s process for degrading and recycling components—and phagosomal acidification, which makes the internal environment of the macrophage more hostile to the bacteria. Furthermore, the steroid appeared to protect the macrophages from dying due to the infection, increasing their survival and thus their capacity to fight the pathogen.
A New Frontier in Host-Directed Therapy
This approach is a prime example of a strategy known as host-directed therapy (HDT). Unlike traditional antibiotics, which directly target and kill bacteria, HDTs aim to modulate the host’s own biological responses to improve disease outcomes. The goals of HDT in tuberculosis are twofold: to enhance the host’s innate ability to eliminate the pathogen and to limit the immunopathology that causes lung damage. The rise of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains has made finding alternative and complementary treatments a global health priority, as conventional antibiotic regimens can last for up to two years and involve toxic drugs.
Rethinking Steroid Use in Clinical Practice
The study’s findings provide a strong rationale for broadening the use of adjunctive steroid therapy in tuberculosis treatment. Professor Joseph Keane of Trinity College Dublin, an author on the study, noted that steroids are currently underused in TB care despite their effectiveness in managing inflammation in severe forms of the disease. The research provides reassurance that dexamethasone not only calms inflammation but also supports the macrophage’s ability to control the infection.
The investigation also uncovered specific metabolic changes induced by the steroid. Dexamethasone was found to reduce glycolysis—a key energy-producing process—in the macrophages. While this limits the total energy available to the cell, it is linked to the reduction in the production of inflammatory cytokines, helping to achieve a more balanced and less damaging immune response. By providing new evidence that steroids can be targeted to support antimicrobial defense while controlling inflammation, this work may help redefine clinical guidelines for their use in a wider range of TB patients.
Addressing a Formidable Public Health Challenge
Tuberculosis remains one of the world’s deadliest infectious diseases. Standard treatment for drug-susceptible TB requires a six-month course of multiple antibiotics. For drug-resistant forms of the disease, the challenge is far greater. According to World Health Organization guidelines, treating MDR-TB can require complex regimens of second-line drugs that are often less effective, more toxic, and must be taken for 18 months or longer. Newer, shorter all-oral regimens are becoming available but are not yet universally accessible.
The lengthy and arduous nature of these treatments contributes to non-adherence, which can lead to treatment failure and the further spread of resistant strains. Complementary treatments like targeted steroid therapy could potentially shorten treatment durations and improve success rates by making the host environment less hospitable for the bacteria and reducing disease severity. By helping to mitigate the severe lung damage caused by the infection, such therapies could significantly improve the long-term health and quality of life for millions of TB survivors globally.
