Researchers from University College London (UCL) have identified a key mechanism that helps the body suppress inflammation — a breakthrough that could lead to new treatments for chronic diseases affecting millions of people worldwide.

Inflammation is the body’s first line of defense against infection and injury, but when it fails to shut down properly, it can lead to serious health problems such as arthritis, heart disease, and diabetes. Until now, scientists did not fully understand how the body decides to switch off the immune “fight” response and begin the healing process.

A study published in Nature Communications shows that tiny molecules derived from fatty tissue, known as epoxy-oxylipins, act as natural brakes on the immune system. These molecules prevent the excessive expansion of certain immune cells called intermediate monocytes, which can drive chronic inflammation associated with tissue damage, disease, and disease progression.

In the study, healthy volunteers received a small injection of ultraviolet-killed E. coli bacteria into the forearm, triggering a short-lived inflammatory response — pain, redness, heat, and swelling — similar to that seen after infection or injury. The volunteers were divided into two groups: a preventive group and a therapeutic group.

At different time points, participants were given the drug GSK2256294, which blocks an enzyme called soluble epoxide hydrolase (sEH), a molecule that naturally breaks down epoxy-oxylipins.

Preventive group: Participants received the drug two hours before inflammation began to determine whether an early increase in epoxy-oxylipins could prevent harmful immune changes, reports Planet Today. This group included 24 volunteers — 12 received the drug and 12 received a placebo.

Therapeutic group: Participants received the drug four hours after inflammation had begun, mimicking real-world treatment after symptoms appear. This group also included 24 volunteers — 12 received the drug and 12 received a placebo.

Both approaches showed that blocking sEH with GSK2256294 increased epoxy-oxylipin levels, accelerated pain resolution, and significantly reduced levels of intermediate monocytes in blood and tissues — immune cells linked to chronic inflammation and disease. Interestingly, the drug had little effect on visible symptoms such as redness and swelling.

Further experiments revealed that one epoxy-oxylipin in particular, 12,13-EpOME, works by suppressing the p38 MAPK protein signaling pathway, which triggers monocyte transformation. This was confirmed both in laboratory experiments and in volunteers who received a drug blocking p38.

“Our findings reveal a natural mechanism that limits the expansion of harmful immune cells and helps inflammation resolve more quickly,” said study co-author Olivia Bracken of University College London. “Targeting this pathway could lead to safer treatments that restore immune balance without suppressing overall immunity.

Given that chronic inflammation is considered one of the major global health threats, this discovery opens up promising opportunities for the development of new therapies.”

“This is the first study to map epoxy-oxylipin activity in humans during inflammation,” added co-author Professor Derek Gilroy, also from University College London. “By increasing levels of these protective fat-derived molecules, we could develop safer treatments for diseases driven by chronic inflammation. This was a fully human-based study with direct relevance to autoimmune diseases, as we used a drug already suitable for use in people — one that could potentially be repurposed to treat flare-ups of chronic inflammatory diseases, an area where effective treatments are currently lacking.”

The researchers chose to study epoxy-oxylipins because animal studies had shown that these fat-derived molecules reduce inflammation and pain, but their role in humans remained unknown. Unlike well-studied inflammatory mediators such as histamine and cytokines, epoxy-oxylipins are part of a poorly understood mechanism that scientists believe may naturally calm the immune system.

The discovery paves the way for clinical trials of sEH inhibitors as potential treatments for conditions such as rheumatoid arthritis and cardiovascular disease.

“For example, rheumatoid arthritis is a disease in which the immune system attacks the cells lining the joints. sEH inhibitors could be tested in combination with existing medications to determine whether they can help prevent or slow joint damage caused by the disease,” Bracken said.

“Pain from arthritis can affect how we move, think, sleep, and feel, as well as our ability to spend time with loved ones. Pain is incredibly complex and influenced by many different factors, and we also know that pain is experienced differently by each person,” said Caroline Aylott, Head of Research at Arthritis UK. “That is why it is vital to invest in research like this, which helps us understand what causes pain and how people experience it. We are encouraged by the results of this study, which identified a natural process capable of stopping inflammation and pain, and we hope it will lead to new pain-relief options for people living with arthritis.”