Scientists at University College London (UCL) have identified how the human body naturally switches off inflammation — a breakthrough that could transform treatment for chronic diseases like arthritis, heart disease, and diabetes. Published in the journal Nature Communications, the study points to a group of fat-derived molecules called epoxy-oxylipins as the immune system’s built-in braking system.
When Inflammation Doesn’t Stop
Inflammation is the body’s first response to infection and injury, mobilizing immune cells to fight threats and begin healing. The problem starts when inflammation fails to shut down on time. Unresolved, ongoing inflammation can damage healthy tissue and fuel a range of serious conditions — including rheumatoid arthritis, cardiovascular disease, and type 2 diabetes. Until this study, scientists had not fully mapped the biological signal that tells the immune system to stand down.
The Molecules Behind the Braking System
The UCL team focused on epoxy-oxylipins, small fat-based compounds produced naturally in the body. Animal research had previously suggested that these molecules could reduce inflammation and pain, but their role in human biology remained unclear. The new study fills that gap.
Epoxy-oxylipins appear to work by limiting the overgrowth of a particular type of immune cell called intermediate monocytes — white blood cells that are helpful in short bursts but harmful in excess. When these cells accumulate beyond what the body needs, they keep the immune system in a state of constant activity, contributing to the chronic inflammation that underlies many serious diseases.
A Controlled Human Experiment
To study this process directly in humans, researchers used a carefully designed experiment. Healthy volunteers each received a small injection of UV-killed E. coli bacteria into the forearm, triggering a short-lived but realistic inflammatory response — pain, redness, heat, and swelling.
Participants were divided into two groups. In the prophylactic arm, volunteers took a drug called GSK2256294 two hours before inflammation began. In the therapeutic arm, others received the same drug four hours after inflammation had already started — mirroring how a treatment would be used in real clinical settings. Each group included 24 participants, with 12 receiving the drug and 12 receiving a placebo. The drug works by blocking an enzyme called soluble epoxide hydrolase (sEH), which normally breaks down epoxy-oxylipins, allowing the protective molecules to accumulate.
Faster Pain Relief, Fewer Harmful Cells
In both groups, participants who received GSK2256294 experienced faster pain resolution and showed significantly lower levels of intermediate monocytes in blood and tissue compared to those given a placebo. The effect held whether the drug was taken before or after inflammation began.
Notably, the treatment did not produce a visible reduction in redness or swelling, suggesting it works at a deeper cellular level rather than on surface symptoms.
Researchers traced the key action to a specific epoxy-oxylipin called 12,13-EpOME, which appears to shut down a signaling protein known as p38 MAPK — the driver behind monocyte transformation. Lab experiments and additional volunteer tests using a p38-blocking drug confirmed this mechanism.
What the Researchers Say
First author Dr. Olivia Bracken, from UCL’s Department of Ageing, Rheumatology and Regenerative Medicine, said the findings “reveal a natural pathway that limits harmful immune cell expansion and helps calm inflammation more quickly.” She added that targeting this mechanism could lead to safer treatments that restore immune balance without broadly suppressing the immune system.
Corresponding author Professor Derek Gilroy, from UCL’s Division of Medicine, called it a landmark finding: “This is the first study to map epoxy-oxylipin activity in humans during inflammation.” He noted that the drug used in the study already exists and is suitable for human use, making it a realistic candidate for repurposing to treat flares in chronic inflammatory conditions.
A Path Toward New Therapies
The discovery opens the door to clinical trials testing sEH inhibitors in patients with conditions like rheumatoid arthritis and cardiovascular disease. Dr. Bracken noted that sEH inhibitors could potentially be trialled alongside existing medications to see whether they help prevent or slow joint damage in rheumatoid arthritis.
The research was funded by Arthritis UK, and Dr. Caroline Aylott, the organization’s Head of Research Delivery, expressed optimism about the future impact. “We are excited to see the results of this study, which has found a natural process that could stop inflammation and pain,” she said, adding hope that the work would lead to new pain management options for people living with arthritis.
The study was a collaborative effort involving researchers from UCL, King’s College London, the University of Oxford, Queen Mary University of London, and the National Institute of Environmental Health Sciences in the United States.
