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Researchers at University College London (UCL) have identified a natural biological mechanism that helps the body switch off inflammation. The discovery could support the development of new treatments for chronic inflammatory diseases, including rheumatoid arthritis, heart disease and diabetes.
Inflammation is an essential immune response that helps the body fight infections and repair damaged tissue. However, when inflammation continues for too long, it can damage healthy cells and contribute to chronic diseases.
Scientists understand many of the processes that initiate inflammation. Less is known about how the body recognizes that a threat has passed and shifts from fighting the problem to repairing tissue.
Epoxyoxylipins may act as a natural brake on inflammation
In a new study published in Nature Communications, researchers identified a group of fat-derived molecules called epoxyoxylipins that appear to help resolve inflammation in humans.
These molecules may act as a natural brake on the immune system by limiting the buildup of intermediate monocytes. These white blood cells can support healing in the short term, but excessive accumulation or prolonged activity may contribute to chronic inflammation.
To study the process in humans, researchers injected healthy volunteers with small amounts of ultraviolet-killed Escherichia coli bacteria in the forearm. Because the bacteria were no longer alive, they could not cause an infection, but they were still able to trigger a temporary inflammatory response.
The volunteers developed common signs of inflammation, including pain, redness, heat and swelling. They were divided into a prevention group and a treatment group.
The researchers administered GSK2256294, a drug that blocks an enzyme called soluble epoxide hydrolase, or sEH. Under normal conditions, sEH breaks down epoxyoxylipins. Blocking the enzyme allows more of these potentially protective molecules to remain in the body.
- Prevention group: Twenty-four volunteers received the drug or a placebo two hours before inflammation was triggered. This allowed researchers to examine whether increasing epoxyoxylipin levels early could prevent harmful immune changes.
- Treatment group: Twenty-four volunteers received the drug or a placebo four hours after inflammation began, providing a model that more closely reflects treatment after symptoms appear.
Drug linked to faster pain relief and fewer inflammatory cells
Both approaches produced similar results. Blocking sEH increased epoxyoxylipin levels, helped resolve pain more quickly and reduced the number of intermediate monocytes detected in the blood and tissue.
These immune cells are believed to play a role in persistent inflammation and the progression of inflammatory diseases. However, the treatment did not significantly change visible symptoms such as redness and swelling. This suggests that the drug may have affected deeper immune processes even when external signs of inflammation remained.
The researchers also investigated how epoxyoxylipins produce their effects. They found that one molecule, 12,13-EpOME, appears to inhibit p38 MAPK, a protein-signaling pathway involved in the development of intermediate monocytes and prolonged inflammatory activity.
The team confirmed the mechanism through laboratory experiments and in volunteers who received drugs that directly block the p38 pathway.
Lead author Dr Olivia Bracken, from UCL’s Department of Aging, Rheumatology and Regenerative Medicine, said: “Our findings reveal a natural pathway that helps limit the proliferation of harmful immune cells and resolves inflammation more quickly.”
“Targeting this mechanism could lead to safer treatments that restore immune balance without broadly suppressing the immune system. As chronic inflammation remains a major global health threat, this discovery opens a promising avenue for future therapies.”
A potential route to safer anti-inflammatory treatments
Many existing treatments for inflammatory and autoimmune diseases work by suppressing parts of the immune system. Although this can reduce inflammation, it may also weaken the body’s ability to defend itself against infections.
The pathway identified in this study could offer a different approach by enhancing the body’s own mechanisms for controlling inflammation.
Corresponding author Professor Derek Gilroy of UCL’s Department of Medicine said: “This is the first study to map epoxyoxylipin activity in humans during inflammation.”
“By strengthening these protective fat molecules, we could potentially design safer treatments for diseases caused by chronic inflammation.”
He added that the study was conducted entirely in humans and used a drug that is already suitable for human use. This could make it possible to investigate whether sEH inhibitors can be repurposed to treat flare-ups of chronic inflammatory conditions.
Why epoxyoxylipins could be important
Researchers focused on epoxyoxylipins because previous animal studies suggested that these molecules could help reduce inflammation and pain. However, their role in humans has been less clear.
Compared with well-known inflammatory substances such as histamine and cytokines, epoxyoxylipins are part of a relatively understudied signaling system. Scientists have suspected that this pathway may help the immune system move naturally from an active inflammatory state toward recovery.
This new human study provides evidence supporting that theory and offers a clearer understanding of how the body may resolve inflammation.
Next steps for chronic inflammation research
The findings could support future clinical trials investigating sEH inhibitors in conditions such as rheumatoid arthritis and cardiovascular disease. More research is needed to determine whether the treatment is safe and effective for people with long-term inflammatory diseases.
Dr Bracken said that rheumatoid arthritis could be one potential area of investigation. In this autoimmune disease, the immune system attacks the tissue lining the joints, causing pain, swelling, stiffness and possible long-term joint damage.
sEH inhibitors could eventually be studied alongside existing rheumatoid arthritis medicines to determine whether they can help reduce inflammation or prevent disease-related damage.
Dr Caroline Ilott, Head of Research at Arthritis UK, said: “Arthritis pain 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.”
“That is why research that improves our understanding of the causes and effects of pain is so important. We are pleased to see this study identify a natural process that helps stop inflammation and pain. In the future, this could lead to new pain-management options for people with arthritis.”
What are intermediate monocytes?
Intermediate monocytes are white blood cells that help fight infections and repair tissue. They can support immune regulation and recovery in the short term, but excessive or prolonged activity may keep the immune system switched on and contribute to chronic inflammation.
The study was funded by Arthritis UK and involved researchers from UCL, King’s College London, the University of Oxford, Queen Mary University of London and the National Institute of Environmental Health Sciences.
Source: www.sciencedaily.com