Researchers at Trinity College Dublin and St. James’s Hospital have demonstrated that dexamethasone, a commonly prescribed anti-inflammatory steroid, reduces harmful inflammation triggered by Mycobacterium avium without weakening the ability of human immune cells to control the infection, according to a study published in the Journal of Infectious Diseases.
Understanding Nontuberculous Mycobacterial Disease and Treatment Challenges
Nontuberculous mycobacterial (NTM) infections present a growing global health challenge, particularly for individuals living with chronic lung disease. Patients diagnosed with these infections typically require prolonged courses consisting of multiple antibiotics. Despite rigorous antimicrobial treatment, many patients continue to experience debilitating symptoms driven by persistent inflammation. Clinicians have traditionally avoided routine steroid use in NTM disease out of caution that suppressing T cell immune responses during an active infection could worsen outcomes.
According to Dr. Donal Cox, senior author of the research from the Trinity Translational Medicine Institute, the study suggests an alternative approach. “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,” Dr. Cox stated.
How Dexamethasone Affects Macrophage Metabolism
To understand the cellular mechanisms at play, Dr. Cox and his research team investigated how human macrophages respond to Mycobacterium avium. Macrophages are specialized immune cells that act as the human body’s first line of defense against invading pathogens. Building on previous research showing that dexamethasone alters the metabolism of macrophages infected with Mycobacterium tuberculosis, the team sought to determine whether similar pathways could be targeted during Mycobacterium avium infection.
Did you know? Advances in immunometabolism research show that immune cell metabolism directly dictates how macrophages respond to bacterial threats. Glycolysis plays a central role in this myeloid metabolic shift during a host response to NTM.
Laboratory findings revealed that treatment with dexamethasone significantly reduced infection-driven macrophage metabolic activity while simultaneously lowering the production of key inflammatory signals. Specifically, the production of inflammatory cytokines—including TNF, IL-1β, IL-6, and IL-8—was markedly reduced following dexamethasone treatment. Crucially, the steroid lowered this inflammatory response without increasing bacterial growth within the immune cells, demonstrating that inflammatory responses can be successfully separated from bacterial control.
Potential Impact on Future Infectious Disease Therapies
Because the Mycobacterium avium complex ranks among the most common causes of NTM lung disease worldwide, identifying adjunct therapies is vital. Chronic inflammation contributes substantially to tissue damage and a reduced quality of life for patients undergoing standard antimicrobial therapy.
According to Dr. Cox, current treatment strategies focus primarily on killing the bacteria, but inflammation itself drives significant patient symptoms. Finding ways to control inflammation without impairing innate immunity offers a potential gateway to more effective therapies. The study provides a strong rationale for investigating steroids as potential host-directed therapies alongside existing antimicrobial treatments, utilizing primary human macrophages and real-time metabolic measurements.
Prof. Joseph Keane, Professor of Medicine at Trinity, noted that this research highlights the central role of glycolysis in the macrophage host response to NTM. These data support the ongoing development of steroids as adjuvant antimicrobial therapies for this condition.
Frequently Asked Questions
What is NTM disease?
Nontuberculous mycobacterial (NTM) disease is an infection caused by environmental bacteria related to tuberculosis, frequently affecting patients with chronic lung conditions and causing persistent inflammation and tissue damage.
Why are steroids traditionally avoided in NTM infections?
Clinicians have historically exercised caution regarding steroid use during infections because suppressing T cell immune responses could potentially weaken the body’s ability to clear pathogens.
What did the Trinity College Dublin study find regarding dexamethasone?
According to the published findings, dexamethasone reduces harmful inflammation and macrophage metabolic activity during Mycobacterium avium infection without compromising the immune cells’ ability to control the bacteria.
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