- Date:
- September 12, 2026
- Source:
- University College London
- Summary:
- Scientists have uncovered a natural braking system that helps the immune system switch off inflammation and prevent harmful immune cells from building up. Boosting this pathway in people reduced inflammation-related immune changes and sped up pain relief, pointing toward potential new treatments for chronic inflammatory diseases.
- Share:
Researchers at University College London (UCL) have identified a biological mechanism that helps the body bring inflammation to an end, a finding that could eventually lead to new treatments for chronic inflammatory diseases affecting millions of people.
Inflammation is one of the immune system's most important defense responses. It helps the body fight infection and repair damaged tissue. But if that response remains active for too long, it can begin to harm healthy tissue and contribute to conditions including arthritis, heart disease, and diabetes.
Scientists have long known a great deal about how inflammation begins. What has been less clear is how the body decides that the danger has passed and shifts from fighting a threat to repairing the damage.
A Natural Brake on the Immune System
The new study, published in Nature Communications, points to a group of small fat-derived molecules called epoxy-oxylipins as part of that shutdown process.
According to the researchers, these molecules act like natural brakes on the immune system. They help prevent excessive growth of intermediate monocytes,* a type of white blood cell that can support healing in the short term but may contribute to chronic inflammation if too many accumulate or remain active for too long.
To study the process directly in people, the researchers gave healthy volunteers a tiny injection of UV-killed E. coli bacteria in the forearm. Because the bacteria were no longer alive, they could not cause an infection, but they still triggered a temporary inflammatory response.
That reaction produced the familiar signs of inflammation, including pain, redness, heat, and swelling, similar to what can happen after an injury or infection.
The volunteers were divided into two groups: prophylactic arm and therapeutic arm.
Researchers then gave participants a drug called GSK2256294 at different stages of the inflammatory response. The drug blocks an enzyme known as soluble epoxide hydrolase (sEH). Under normal conditions, sEH breaks down epoxy-oxylipins, so blocking the enzyme allows more of these protective molecules to remain in the body.
- Prophylactic arm: Participants received the drug two hours before inflammation began, allowing researchers to test whether increasing epoxy-oxylipins early could prevent harmful immune changes. In this group, there were 24 volunteers -- 12 were treated, 12 untreated (placebo).
- Therapeutic arm: Participants received the drug four hours after inflammation started, better reflecting how a treatment might be used after symptoms have already appeared. In this group, there were 24 volunteers -- 12 were treated, 12 untreated (placebo).
Pain Resolved Faster and Harmful Immune Cells Fell
Both approaches produced similar results.
Blocking sEH increased epoxy-oxylipin levels, helped pain resolve more quickly, and sharply reduced the number of intermediate monocytes found in both the blood and tissue. These immune cells have been linked to persistent inflammation and the progression of inflammatory disease.
The treatment did not, however, significantly change outward signs such as redness or swelling. That suggests the drug may have been altering deeper immune processes even when visible symptoms remained largely unchanged.
The researchers then investigated how the effect worked at the molecular level.
They found that one epoxy-oxylipin, 12,13-EpOME, appears to suppress a protein signaling pathway known as p38 MAPK. This pathway helps drive the transformation of monocytes into the intermediate form associated with prolonged inflammatory activity.
The team confirmed the mechanism in laboratory experiments and in volunteers who received a drug that directly blocks p38.
First author Dr. Olivia Bracken (UCL Department of Ageing, Rheumatology and Regenerative Medicine) said: "Our findings reveal a natural pathway that limits harmful immune cell expansion and helps calm inflammation more quickly.
"Targeting this mechanism could lead to safer treatments that restore immune balance without suppressing overall immunity. With chronic inflammation ranked as a major global health threat, this discovery opens a promising avenue for new therapies."
A Possible Route to Safer Anti-Inflammatory Treatments
Many existing treatments for inflammatory and autoimmune diseases work by suppressing parts of the immune system. While that can reduce inflammation, it can also interfere with the body's ability to defend itself.
The pathway identified in the new study may offer another strategy: strengthening a natural process the body already uses to bring inflammation under control.
Corresponding author Professor Derek Gilroy (UCL Division of Medicine) said: "This is the first study to map epoxy-oxylipin activity in humans during inflammation.
"By boosting these protective fat molecules, we could design safer treatments for diseases driven by chronic inflammation."
He added: "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."
Why Epoxy-Oxylipins Matter
Researchers focused on epoxy-oxylipins because earlier animal studies had suggested that these molecules can reduce inflammation and pain.
Their role in humans, however, had remained much less clear.
Compared with better-known inflammatory substances such as histamine and cytokines, epoxy-oxylipins belong to a relatively underexplored signaling system. Scientists suspected that this pathway might help the immune system naturally transition from an active inflammatory state toward recovery.
The new human study provides direct evidence supporting that idea.
Next Steps
The findings could pave the way for clinical trials testing sEH inhibitors in chronic inflammatory conditions, including rheumatoid arthritis and cardiovascular disease.
Dr. Bracken said: "For instance, rheumatoid arthritis is a condition in which the immune system attacks the cells that line your joints. sEH inhibitors could be trialed alongside existing medications to investigate if they can help prevent or slow down joint damage incurred by the condition."
Rheumatoid arthritis is an autoimmune disease in which the immune system mistakenly attacks tissue around the joints, causing pain, swelling, stiffness, and potentially long-term damage.
Dr. Caroline Aylott, Head of Research Delivery at Arthritis UK, said: "The pain of arthritis can affect how we move, think, sleep and feel, along with our ability to spend time with loved ones. 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.
"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."
* Intermediate monocytes are white blood cells that help fight infection and repair tissue. In short bursts, they help coordinate the immune response and support recovery, but if they persist or grow in excess, they keep the immune system switched on, leading to chronic inflammation.
The study was funded by Arthritis UK and involved researchers at UCL, King's College London, University of Oxford, Queen Mary University of London, and National Institute of Environmental Health Sciences, USA.
Story Source:
Materials provided by University College London. Note: Content may be edited for style and length.
Journal Reference:
- Olivia V. Bracken, Parinaaz Jalali, James R. W. Glanville, Larrissa Benvenutti, Emma S. Chambers, Hugh Trahair, Madhur Motwani, Karen T. Feehan, Jamie G. Evans, Jhonatan de Souza Carvalho, Roel P. H. De Maeyer, Arne N. Akbar, Fred B. Lih, Darryl C. Zeldin, David Bishop-Bailey, Matthew L. Edin, Derek W. Gilroy. Epoxy-oxylipins direct monocyte fate in inflammatory resolution in humans. Nature Communications, 2026; 17 (1) DOI: 10.1038/s41467-025-67961-5
Cite This Page:
Facts Only
Researchers from University College London, King's College London, University of Oxford, Queen Mary University of London, and the National Institute of Environmental Health Sciences conducted the study.
The study was published in Nature Communications on September 12, 2026.
Arthritis UK provided funding for the research.
The study identified epoxy-oxylipins as molecules that limit the growth of intermediate monocytes.
Healthy volunteers received injections of UV-killed E. coli bacteria to trigger inflammation.
48 volunteers participated: 24 in a prophylactic arm and 24 in a therapeutic arm.
The drug GSK2256294 was administered to block the enzyme soluble epoxide hydrolase (sEH).
Treatment resulted in faster pain resolution and reduced intermediate monocyte counts in blood and tissue.
The treatment did not significantly change redness or swelling.
12,13-EpOME was identified as the specific epoxy-oxylipin that suppresses the p38 MAPK signaling pathway.
Executive Summary
Researchers have identified a biological "braking system" that allows the body to resolve inflammation by utilizing fat-derived molecules called epoxy-oxylipins. By blocking the enzyme soluble epoxide hydrolase (sEH), scientists increased the levels of these molecules in human volunteers, which accelerated pain relief and reduced the accumulation of intermediate monocytes—white blood cells associated with chronic inflammatory states.
The study employed a dual-track approach, testing the drug both before and after the onset of inflammation. While the treatment effectively altered deep immune processes and reduced pain, it did not visibly reduce surface-level symptoms like swelling or redness. This suggests the mechanism operates on a cellular level rather than through immediate physical suppression.
These findings suggest a potential shift in treating autoimmune and chronic inflammatory diseases, such as rheumatoid arthritis. Rather than suppressing the entire immune system—which can leave patients vulnerable to infection—this approach seeks to enhance a natural recovery process. However, moving from controlled volunteer trials to clinical treatment for complex chronic diseases remains a future objective.
Full Take
This study employs a rigorous experimental design, utilizing a randomized, placebo-controlled human model with both prophylactic and therapeutic arms. A peer reviewer would likely note the small sample size (n=48), which is typical for early-phase mechanistic studies but insufficient for broad clinical claims. The use of UV-killed E. coli provides a clean, controlled inflammatory trigger, though it may not perfectly replicate the systemic complexity of an autoimmune flare.
The data demonstrates a clear reduction in intermediate monocytes and reported pain, yet the disconnect between these markers and visible symptoms (redness/swelling) is a critical nuance. The authors correctly frame the findings as a "natural pathway," but the leap from a temporary bacterial trigger to the treatment of chronic conditions like rheumatoid arthritis is a significant extrapolation. The efficacy of sEH inhibitors in a state of permanent dysregulation is not yet proven.
The findings extend prior animal data into human application, confirming the role of 12,13-EpOME in suppressing the p38 MAPK pathway. This challenges the paradigm of "suppression-based" anti-inflammatories, proposing instead a "resolution-based" model.
Bridge Questions:
1. How does the efficacy of sEH inhibitors differ when inflammation is triggered by an autoimmune malfunction versus an external pathogen?
2. Would long-term elevation of epoxy-oxylipins interfere with other necessary immune functions beyond the resolution of inflammation?
Counterstrike Scan:
A coordinated influence campaign would use this to claim a "cure for arthritis" is imminent to drive investment or pharmacy stocks. The actual content remains measured, focusing on cellular mechanisms and the need for future clinical trials.
Patterns detected: none