Steroids reduce inflammation in chronic mycobacterial lung infections without limiting antimicrobial defense
· Medical Xpressedited by Sadie Harley, reviewed by Alexander Pol
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Researchers from Trinity College Dublin and St. James's Hospital have shown that dexamethasone, a commonly prescribed anti-inflammatory steroid, can reduce harmful inflammation triggered by Mycobacterium avium without weakening the ability of human immune cells to control the infection.
The findings, published in the Journal of Infectious Diseases, suggest dexamethasone may offer a new adjuvant approach for better managing nontuberculous mycobacterial (NTM) disease.
NTM infections present a growing global health challenge, particularly among people with chronic lung disease. Treatment often requires prolonged courses of multiple antibiotics, yet many patients continue to experience symptoms driven by persistent inflammation. Steroids are not routinely used in NTM disease because clinicians have traditionally been cautious about suppressing T-cell immune responses during infection.
"Our study suggests that it may be possible to fine-tune this response by reducing damaging inflammation while still preserving the immune defenses that help control infection," said Dr. Donal Cox, senior author of the research.
Cox and the research team, based at the Trinity Translational Medicine Institute, investigated how human macrophages, specialized immune cells that act as a first line of defense against infection, respond to Mycobacterium avium.
They found that treatment with dexamethasone significantly reduced infection-driven macrophage metabolic activity while also lowering the production of inflammatory signals. Importantly, the steroid reduced the inflammatory response but did not increase bacterial growth within these key immune cells.
Why did the team undertake this research?
Advances in immunometabolism research have shown that immune cell metabolism plays an important role in determining how macrophages respond to infection. While this has been well studied in infectious diseases such as tuberculosis, very little is known about how metabolism influences immune responses to NTM.
The Trinity research group has previously demonstrated that dexamethasone alters the metabolism of macrophages infected with Mycobacterium tuberculosis. They therefore wanted to determine whether similar pathways could be targeted during Mycobacterium avium infection and whether inflammation could be reduced without compromising the body's natural ability to control infection.
Key findings
- Production of inflammatory cytokines TNF, IL-1β, IL-6 and IL-8, which increase inflammation, is markedly reduced following dexamethasone treatment.
- Macrophages treated with dexamethasone retain their ability to control Mycobacterium avium.
- The findings demonstrate that inflammatory responses can be separated from bacterial control in human macrophages.
Potential impact of this research
NTM infections are increasing worldwide, and Mycobacterium avium complex is among the most common causes of NTM lung disease. Patients require lengthy multidrug antibiotic therapy, and chronic inflammation can contribute substantially to symptoms and reduced quality of life, even while on effective antimicrobial treatment.
As a result, new treatment options are badly needed.
"Current treatment strategies for NTM disease focus primarily on killing the bacteria," Cox said. "However, inflammation itself can contribute significantly to symptoms and tissue damage in patients, so finding ways to control inflammation without impairing antimicrobial innate immunity offers a potential gateway to much more effective therapies."
"This study provides evidence that dexamethasone may be able to do this. And although further studies are needed, our findings are exciting because they provide a strong rationale for investigating steroids as potential host-directed therapies in addition to existing antimicrobial treatments."
Because this study used primary human macrophages and real-time metabolic measurements to investigate how corticosteroids influence immune metabolism during Mycobacterium avium infection, the researchers are especially hopeful that it could be effectively applied in real-life situations.
Professor Joseph Keane, professor of medicine at Trinity, added, "This research demonstrates the central role of glycolysis in the macrophage host response to NTM. This myeloid metabolic shift is sufficient but not necessary for macrophage antimicrobial effect. These data support developing steroids as adjuvant antimicrobial therapies for this important disease."
Publication details
Journal of Infectious Diseases (2026). DOI: 10.1093/infdis/jiag394
Journal information: Journal of Infectious Diseases
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Infectious diseasesPulmonary medicine Provided by Trinity College Dublin Who's behind this story?
Sadie Harley
BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →
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PhD nano-engineering from Delft University. Published researcher and journal reviewer. Brings scientific insight to content standards. Full profile →
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