Research suggests that an irregular body clock plays a key role in driving inflammation within the immune cells.

The latest research from RCSI has revealed that the body’s irregular clock can cause inflammation, which can lead to the most serious and prevalent diseases in humans.

Published in Frontiers in Immunology, the research was conducted by the School of Pharmacy and Biomolecular Sciences at RCSI University of Medicine and Health Sciences.

The circadian body clock creates 24 hour rhythms that keep people well and in sync with the night/day cycle. This involves regulating the rhythm of the body’s own (innate) immune cells, also known as macrophages. Cell rhythms can be altered by factors such as shift work, irregular eating, sleeping patterns or shift work. Cells then produce molecules that cause inflammation. This can result in chronic inflammation conditions like heart disease, obesity , and diabetes, as well as the ability of our body to fight off infections.

The researchers looked at macrophages which are the most important immune cells. They tested them under laboratory conditions. They wanted to find out if macrophages that do not have a body clock, use or metabolize fuel differently and could this be the reason why they produce more inflammatory substances.

Researchers discovered that macrophages that had no body clock absorbed much more glucose and were capable of breaking it down much more quickly than normal cells. They also discovered that in the mitochondria (the cells energy powerhouse), the pathways by which glucose was further broken into energy production were quite different in macrophages that did not have a clock. This led to the creation of reactive oxygen substances (ROS), which further stimulated inflammation.

Dr George Timmons, lead author of the study, said: “Our results add to the growing body of research that demonstrates how disruption to our body clock can lead to inflammation and infection, and one of the aspects is fuel usage at the level of key immune cells such as macrophages.”

This study also showed that anything that can negatively affect our body clocks (such as lack of sleep or insufficient sunlight) can affect our ability to function effectively.

Dr Annie Curtis is Senior Lecturer at the RCSI School of Pharmacy and Biomolecular Sciences and a senior author on the paper.

RCSI collaborated with researchers from Swansea University and Trinity College Dublin to conduct the study.

Journal reference:

Timmons, G.A. et. and. (2021). The Circadian Clock Protein BMAL1 Functions as a Metabolic Sensor in Macrophages to Limit Pro IL-1b Production Frontiers in Immunology.

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Gemma Wilson

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