Researchers from Trinity College Dublin and St James’s Hospital have shown that dexamethasone can reduce harmful inflammation triggered by Mycobacterium avium.
A common steroid may help reduce the harmful impacts of an infection caused by bacteria found in soil, dust and water, an Irish study suggests.
Researchers from Trinity College Dublin and St James’s Hospital have shown that dexamethasone can reduce harmful inflammation triggered by Mycobacterium avium.
The bacteria, which lives naturally in soil, dust and water, is one of the most common causes of nontuberculous mycobacterial (NTM) disease. The illness can cause lung infections or widespread systemic poor health, particularly in people with weakened immune systems or pre-existing lung conditions.
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.
Steroids are not routinely used in NTM disease because clinicians have traditionally been cautious about suppressing T-cell immune responses during infection. However, this new study gives hope that common anti-inflammatory steroids may act as an effective adjuvant therapy in tackling the illness.
“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 just been published in the Journal of Infectious Diseases.
“Current treatment strategies for NTM disease focus primarily on killing the bacteria. 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,” added Dr Cox.
“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.”
Dr Cox and the research team, based in the Trinity Translational Medicine Institute, previously demonstrated that dexamethasone alters the metabolism of macrophages infected with Mycobacterium tuberculosis
In this study they 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. The steroid reduced the inflammatory response but did not increase bacterial growth within these key immune cells.
“This research demonstrates the central role of glycolysis in the macrophage host response to NTM,” said Trinity’s professor of medicine Prof Joseph Keane.
“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.”
The research was supported by the Royal City of Dublin Hospital Trust.
Read the study: Dexamethasone reduces glycolysis and inflammation in human macrophages infected with Mycobacterium avium without compromising bacterial control – The Journal of Infectious Diseases.