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 suggest dexamethasone may thus offer a new adjuvant approach for better managing non-tuberculous 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 defences that help control infection,” said Trinity’s Dr Donal Cox, senior author of the research, which has been published in the Journal of Infectious Diseases.
Dr Cox and the research team, based in the Trinity Translational Medicine Institute, investigated how human macrophages, specialised immune cells that act as a first line of defence 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.
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.
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 for patients, 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,” said Dr Cox. “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.”
