Scientists find a natural ‘off switch’ for inflammation in humans

Inflammation can feel like a small storm inside your body. It brings heat, swelling, and pain as the immune system rushes to protect you. Most of the time, that storm fades. But for millions of people, it does not. When inflammation lingers, it can help fuel arthritis, heart disease, diabetes, and other long-term illnesses. A new human study from researchers at University College London offers a clearer look at how the body normally tells the immune system to stand down and start repairing.

The research points to a set of tiny fat-derived molecules called epoxy-oxylipins. The team found these molecules act like natural brakes. They help stop an overgrowth of immune cells called intermediate monocytes, which are linked to chronic, damaging inflammation. The work also suggests a path toward treatments that calm inflammation without shutting down immune defenses.

First author Dr. Olivia Bracken of the UCL Department of Ageing, Rheumatology and Regenerative Medicine described the core finding in simple terms. “Our findings reveal a natural pathway that limits harmful immune cell expansion and helps calm inflammation more quickly,” she said.

To watch inflammation rise and fall in real time, the researchers used a carefully controlled test in healthy volunteers. Each person received a tiny injection of UV-killed E. coli bacteria into the forearm. The bacteria could not cause infection, but it still triggered a short-lived inflammatory response. Volunteers experienced familiar symptoms: pain, redness, heat, and swelling, similar to what happens after infection or injury.

This design mattered. Many studies on inflammation rely on animals or lab dishes. Here, the team tracked inflammation inside the human body, while it unfolded.

Participants were split into two groups that mirrored two real-world approaches to care. One group received treatment before inflammation started, like prevention. The other received it after symptoms began, like a typical clinic visit.

The drug used was GSK2256294. It blocks an enzyme called soluble epoxide hydrolase, also called sEH. Under normal conditions, sEH breaks down epoxy-oxylipins. When sEH is blocked, levels of epoxy-oxylipins rise.

In the prophylactic arm, 24 volunteers took part. Twelve received the drug and 12 received placebo. They were given the drug two hours before inflammation began. This tested whether boosting epoxy-oxylipins early could stop harmful immune changes from ramping up.

In the therapeutic arm, another 24 volunteers took part. Again, 12 received the drug and 12 received placebo. This time, the drug was given four hours after inflammation began. This better matched how many people receive care, after symptoms appear.

Across both approaches, blocking sEH increased epoxy-oxylipin levels. It also sped up pain resolution and sharply reduced levels of intermediate monocytes in blood and tissue. These are immune cells that can help with short-term defense but can become harmful when they persist or expand too much.

The researchers saw one more important detail. The drug did not significantly change outward signs like redness and swelling. That contrast suggests the treatment affected internal immune behavior and pain pathways more than visible skin changes.

Intermediate monocytes are a type of white blood cell. In small bursts, they can help fight infection and support repair. But if they keep rising and sticking around, they can keep the immune system in a constant “on” position. Over time, that can contribute to tissue damage and disease progression.

The study suggests epoxy-oxylipins help prevent that harmful build-up. They appear to limit the shift of monocytes into the intermediate form, steering the immune response toward resolution.

Corresponding author Professor Derek Gilroy of the UCL Division of Medicine called the work a first. “This is the first study to map epoxy-oxylipin activity in humans during inflammation,” he said.

He also emphasized why the approach stands out. “This was an entirely human-based study with direct relevance to autoimmune diseases, as we used a drug already suitable for human use; one that could be repurposed to treat flares in chronic inflammatory conditions, an area currently bereft of effective therapies,” Gilroy said.

The team did not stop at measuring symptoms and immune cell counts. They also asked how these fat-derived molecules deliver their calming message.

Further tests pointed to one epoxy-oxylipin in particular: 12,13-EpOME. The researchers found it works by shutting down a protein signal called p38 MAPK. This signal helps drive monocyte transformation. When p38 MAPK stays active, more intermediate monocytes can develop. When it is suppressed, that shift slows down.

The researchers confirmed this mechanism in lab experiments. They also supported it in volunteers given a p38-blocking drug, which produced similar effects on monocyte changes. That extra step strengthened the idea that epoxy-oxylipins calm inflammation by targeting a specific signaling pathway, rather than broadly dampening the immune system.

Epoxy-oxylipins have not received the same attention as classic inflammatory players like histamine and cytokines. Yet animal studies had already hinted they can reduce inflammation and pain. What remained unclear was whether this pathway plays a similar role in humans.

This study suggests it does. It also suggests the pathway is not just a side effect. It may be part of the body’s built-in plan for ending inflammation safely.

Bracken highlighted the potential clinical value. “Targeting this mechanism could lead to safer treatments that restore immune balance without suppressing overall immunity,” she said. “With chronic inflammation ranked as a major global health threat, this discovery opens a promising avenue for new therapies.”

The study was funded by Arthritis UK. It involved researchers at 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.

Dr. Caroline Aylott, Head of Research Delivery at Arthritis UK, spoke to the human cost behind the science. “The pain of arthritis can affect how we move, think, sleep and feel, along with our ability to spend time with loved ones,” she said. “Pain is incredibly complex and is affected by many different factors. We also know that everybody’s pain is different.

“That is why it is important that we invest in research like this, that helps us understand what causes and influences people’s experience of pain,” Aylott shared with The Brighter Side of News. “We are excited to see the results of this study which has found a natural process that could stop inflammation and pain. We hope in the future that this will lead to new pain management options for people with arthritis.”

This study outlines a promising strategy for treating chronic inflammatory diseases by supporting the body’s own resolution system. Instead of broadly suppressing immunity, boosting epoxy-oxylipins could reduce the specific immune cell shifts that help inflammation linger. That approach could matter for conditions marked by recurring flares, where patients need relief without becoming more vulnerable to infection.

Because the work used a drug already suitable for human use, it may shorten the path toward clinical trials. The researchers suggest sEH inhibitors could be tested for diseases driven by chronic inflammation, including rheumatoid arthritis and cardiovascular disease. Dr. Bracken noted that sEH inhibitors could be trialed alongside existing medications to see whether they help prevent or slow joint damage in rheumatoid arthritis.

For researchers, the findings open a more detailed map of how inflammation ends in humans. That can guide new studies on pain resolution, immune cell behavior, and treatment timing. For patients, the long-term hope is a new class of therapies that calm harmful inflammation while preserving the immune system’s ability to protect and repair.

Research findings are available online in the journal Nature Communications.

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