New research from RCSI University of Medicine and Health Sciences has uncovered how the body’s internal clock, or circadian rhythm, regulates inflammation in the immune system. The findings reveal that immune cells called macrophages behave differently depending on the time of day, paving the way for treatments that work harmoniously with the body’s natural rhythms.
Macrophages are immune cells that act as first responders, detecting harmful substances and triggering inflammation when needed. They assemble large protein complexes called inflammasomes, which function like “smoke detectors” to alert the immune system to potential danger.
The study, published in The FASEB Journal, showed that activating a specific inflammasome called NLRP3 fluctuates based on the 24-hour circadian clock. This rhythm determines when macrophages are most effective at detecting threats and have the energy to respond. A critical driver of this process is the mitochondria, often referred to as the cell’s “powerhouses,” which fuel these immune responses.
Inflammation and the Time of Day
“When macrophages ‘think’ it’s morning, their inflammasome activation is faster and stronger,” explained Professor Annie Curtis, the study’s principal investigator from RCSI’s School of Pharmacy and Biomolecular Sciences. “This heightened immune response aligns with the early part of the day, when we are awake and more likely to face injuries or infections.”
This discovery helps explain why symptoms of inflammatory conditions, such as arthritis, tend to worsen in the morning.
“Overactive inflammasomes are a key factor in diseases like arthritis,” said Dr. James O’Siorain, lead author of the study. “Our findings suggest that therapies targeting these inflammasomes could be more effective when timed to the body’s natural immune rhythms.”
Implications for Treatment
The research opens up possibilities for tailoring treatments for inflammatory diseases based on the time of day. For example, medications designed to regulate inflammasome activity might be most effective when administered during peak macrophage activity in the morning.
The study highlights how an improved understanding of the connection between circadian rhythms and immune function could lead to more precise and effective therapies for inflammation-induced conditions.
Supported by funding from Taighde Éireann – Research Ireland, this study underscores the importance of timing in medicine, offering a new perspective on managing diseases where inflammation plays a central role.