By Morgan Nwanguma
Researchers at University College London (UCL) have identified a biological mechanism that helps the body bring inflammation under control, a discovery that could open the door to new treatments for chronic inflammatory diseases.
The study, published in Nature Communications, found that boosting a group of naturally occurring molecules called epoxy-oxylipins helped reduce harmful immune-cell changes and accelerate pain relief in healthy volunteers.
How the Body Controls Inflammation
Inflammation is a vital part of the immune system’s defence against infection and tissue damage. However, when it persists for too long, it can damage healthy tissue and contribute to diseases such as arthritis, heart disease and diabetes.
While scientists understand many of the processes that trigger inflammation, the mechanisms that bring the response to an end have been less well understood.
The new research sheds light on how the body may naturally switch from fighting a threat to repairing damaged tissue.
Epoxy-Oxylipins: The Immune System’s Natural Brakes
The researchers focused on epoxy-oxylipins, small fat-derived molecules that appear to help regulate inflammation.
These molecules may prevent the excessive accumulation of intermediate monocytes, a type of white blood cell involved in fighting infection and repairing tissue. Although useful during short-term inflammation, excessive or prolonged activity by these cells may contribute to chronic inflammatory conditions.
To investigate the process in humans, the researchers injected healthy volunteers with a small amount of ultraviolet-killed E. coli bacteria in the forearm. The bacteria could not cause an infection but were able to trigger a temporary inflammatory response, producing symptoms such as pain, redness, heat and swelling.
The 48 participants were divided into two groups:
- Prophylactic group: Twenty-four volunteers received the drug GSK2256294 two hours before inflammation was induced. Twelve received the drug, while the remaining 12 received a placebo.
- Therapeutic group: Another 24 volunteers received the drug four hours after inflammation began. This group also consisted of 12 treated participants and 12 placebo recipients.
GSK2256294 blocks soluble epoxide hydrolase (sEH), an enzyme that normally breaks down epoxy-oxylipins. By inhibiting sEH, researchers aimed to increase the levels of these potentially protective molecules in the body.
Faster Pain Relief and Fewer Inflammatory Cells
Both treatment approaches produced similar findings.
Blocking sEH increased epoxy-oxylipin levels, accelerated the resolution of pain and substantially reduced intermediate monocytes in the blood and tissues of the volunteers.
However, the drug did not significantly alter visible signs of inflammation, such as redness or swelling. This suggests that it may have influenced underlying immune processes without producing an obvious change in outward symptoms.
The researchers also examined how the treatment worked at the molecular level.
They identified one epoxy-oxylipin, 12,13-EpOME, as a possible regulator of the p38 MAPK signalling pathway. This pathway is involved in the transformation of monocytes into the intermediate form associated with prolonged inflammatory activity.
Laboratory experiments and additional tests involving a drug that directly blocks p38 supported the proposed mechanism.
Dr Olivia Bracken, from UCL’s Department of Ageing, Rheumatology and Regenerative Medicine and the study’s first author, said the findings revealed a natural pathway that limits harmful immune-cell expansion and helps calm inflammation more quickly.
She added that targeting this mechanism could eventually lead to treatments that restore immune balance without broadly suppressing the immune system.
Could This Lead to Safer Treatments?
Many existing treatments for inflammatory and autoimmune diseases work by suppressing immune activity. Although effective in reducing inflammation, some can also interfere with the body’s ability to fight infections.
Other research has also explored ways to reduce inflammation, including a study that found that a specially formulated tomato-soy juice lowered certain inflammatory markers after four weeks.
The pathway identified by the UCL researchers offers a different approach: enhancing a natural process that helps the body resolve inflammation.
Professor Derek Gilroy, from UCL’s Division of Medicine and the study’s corresponding author, said the research was the first to map epoxy-oxylipin activity in humans during inflammation.
He suggested that boosting these molecules could help scientists develop new treatments for diseases driven by chronic inflammation. He also noted that the study used a drug already suitable for human use, raising the possibility of exploring whether it could be repurposed for inflammatory disease.
However, the research was conducted in healthy volunteers using a controlled, short-term inflammatory response. Its findings do not yet establish that sEH inhibitors can treat chronic diseases or that they are safe and effective for long-term use.
Implications for Rheumatoid Arthritis
The researchers believe the findings could eventually support clinical trials investigating sEH inhibitors in conditions such as rheumatoid arthritis and cardiovascular disease.
Dr Bracken suggested that rheumatoid arthritis could be an area for future research, including studies of whether sEH inhibitors might be used alongside existing medicines to help prevent or slow joint damage.
Rheumatoid arthritis is an autoimmune disease in which the immune system mistakenly attacks tissues around the joints, causing pain, swelling, stiffness and, in some cases, lasting damage.
Dr Caroline Aylott, Head of Research Delivery at Arthritis UK, welcomed the study’s focus on understanding the causes and influences of pain.
She noted that arthritis pain can affect movement, sleep, thinking, emotional wellbeing and relationships, and that pain experiences vary from person to person. She expressed hope that research into natural processes regulating inflammation could eventually lead to new pain-management options.
What Happens Next?
The UCL findings provide new insight into how the human body may naturally resolve inflammation. By identifying a pathway involving epoxy-oxylipins, sEH and p38 MAPK, the research points to a possible new direction for anti-inflammatory drug development.
Further studies, including clinical trials in people with chronic inflammatory diseases, will be needed to determine whether this approach can deliver meaningful, safe and lasting benefits for patients.
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.
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