Researchers at University College London have discovered how the body naturally shuts down inflammation using fat-derived molecules called epoxy-oxylipins. These molecules prevent the buildup of immune cells linked to chronic diseases like arthritis and heart disease. A study involving a drug that boosts these molecules showed faster pain relief and reduced harmful immune activity.
Inflammation serves as the body's defense against infection and injury, but prolonged activity can lead to conditions such as arthritis, heart disease, and diabetes. Until recently, the mechanism for transitioning from immune response to healing was unclear. A study published in Nature Communications details how epoxy-oxylipins regulate this process by limiting intermediate monocytes, white blood cells associated with chronic inflammation.
The research involved healthy volunteers who received an injection of UV-killed E. coli bacteria in the forearm, inducing temporary inflammation with symptoms like pain, redness, heat, and swelling. Participants were split into prophylactic and therapeutic groups. In the prophylactic arm, 24 volunteers—12 treated with the drug GSK2256294 and 12 given placebo—received treatment two hours before inflammation. The therapeutic arm included another 24 volunteers, treated four hours after inflammation began.
GSK2256294 inhibits soluble epoxide hydrolase (sEH), an enzyme that breaks down epoxy-oxylipins, thereby increasing their levels. Treated participants experienced quicker pain resolution and lower counts of intermediate monocytes in blood and tissue, without altering visible symptoms like redness or swelling. One epoxy-oxylipin, 12,13-EpOME, was found to suppress the p38 MAPK signaling pathway, which influences monocyte transformation.
First author Dr. Olivia Bracken from UCL's Department of Ageing, Rheumatology and Regenerative Medicine stated: "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."
Corresponding author Professor Derek Gilroy from UCL's Division of Medicine noted: "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."
The human-based study used a drug suitable for repurposing in autoimmune conditions. Funded by Arthritis UK, it involved collaborators from King's College London, University of Oxford, Queen Mary University of London, and the National Institute of Environmental Health Sciences in the USA. Dr. Caroline Aylott, Head of Research Delivery at Arthritis UK, commented: "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."
Future clinical trials may explore sEH inhibitors for rheumatoid arthritis and cardiovascular disease.
