Researchers at University College London (UCL) in the UK announced on the 19th that they have identified an important biological process that contributes to ending inflammation. The team discovered that fat-derived small molecules called epoxy-oxylipins act as natural inhibitors of immune activity and prevent the accumulation of certain immune cells, intermediate monocytes, which promote chronic inflammation, leading to tissue damage and disease progression.
In a human study involving 48 healthy volunteers, administration of a drug that blocks the sEH enzyme increased epoxyoxylipin levels, accelerated pain relief, and significantly reduced median monocytes. This discovery paves the way for the development of new treatments as chronic inflammation continues to be a major global health threat. This study was published in an international academic journal
Natural inhibition pathway discovered through human experiments
Inflammation is the body’s front line defense system against infection and damage. However, if this reaction is not stopped in a timely manner, it can lead to serious diseases including arthritis, heart disease, and diabetes. Scientists have long known that the immune system must switch from fight to recovery, but the signals that drive this switch are not fully understood.
The research team chose epoxyoxylipin as the research subject. Although these fat-derived molecules are known to reduce inflammation and pain in animal studies, their role in humans is still unknown. Unlike well-studied inflammatory mediators such as histamine or cytokines (signaling substances that cause inflammation), epoxyoxylipins were part of an unexplored pathway that scientists believed could calm the immune system naturally.
To observe this process in humans, the researchers induced a controlled, transient inflammatory response in healthy volunteers. Participants were injected with small doses of UV-killed E. coli into their forearms, which resulted in a short-term reaction characterized by pain, redness, warmth and swelling similar to what can occur after an infection or injury.
48 volunteers were assigned to two groups: prevention group and treatment group. Each group consisted of 24 people, with 12 people divided into the treatment group and 12 people into the placebo group (control group). At a set point in time, participants were administered a drug called GSK2256294. This drug blocks soluble epoxide hydrolase (sEH, an enzyme that normally breaks down epoxyoxylipins).
The preventive group received the drug two hours before the onset of inflammation, testing whether raising epoxyoxylipin levels early could limit harmful immune changes. The treatment group received the drug 4 hours after the onset of inflammation, reflecting treatment after symptom onset.
In both groups, blocking sEH with GSK2256294 increased epoxyoxylipin levels, accelerated pain relief, and significantly reduced intermediate monocytes in the blood and tissues. This drug did not significantly change external symptoms such as redness or swelling.
Faster pain relief and reduction of inflammatory cells
Additional experiments revealed that 12,13-EpOME, one of the epoxyoxylipins, acts by blocking a protein signaling pathway called p38 MAPK (intracellular signaling protein), which promotes monocyte transformation. This was confirmed through laboratory experiments and studies on volunteers who received p38 blockers.
First author Dr Olivia Bracken (UCL Department of Aging, Rheumatology and Regenerative Medicine) said: “These findings reveal a natural pathway that helps limit the proliferation of harmful immune cells and calm inflammation more quickly. Targeting this mechanism could lead to the development of safer treatments that restore immune balance without suppressing overall immunity.”
Corresponding author Professor Derek Gilroy (UCL Faculty of Medicine) said, “This study is the first to identify the activity of epoxyoxylipin in humans during inflammation. By enhancing these protective fat molecules, we may be able to design safer treatments for diseases caused by chronic inflammation.”
“This is a completely human study and is directly related to autoimmune diseases. Because we have already used a drug that is suitable for human use, this is a drug that can be repurposed to treat the exacerbating symptoms of chronic inflammatory diseases, an area that currently lacks effective treatments,” he explained.
This discovery paves the way for clinical trials exploring 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,” said Dr. Bracken. “SEH inhibitors could be tested in combination with existing drugs to see if they could prevent or slow joint damage caused by the disease.”
Dr Caroline Ailot, head of research at Arthritis UK, said: “We are delighted to see the results of this study, which has discovered a natural process that can stop inflammation and pain. We hope this research will lead to new pain management options for people with arthritis.”
