UCL Scientists Discover Natural Braking Mechanism That Shuts Down Chronic Inflammation
Researchers at University College London published findings in Nature Communications identifying fat-derived molecules called epoxy-oxylipins as natural brakes on the immune system. By boosting these molecules in human volunteers, scientists achieved faster pain relief and reduced accumulation of harmful immune cells without broadly suppressing immunity.
Researchers at University College London published findings in Nature Communications identifying a natural mechanism that tells the immune system to stand down after an inflammatory response. The study, led by Professor Derek Gilroy and Dr. Olivia Bracken, focuses on fat-derived signaling molecules called epoxy-oxylipins.
These molecules act as brakes on the immune system. They inhibit the overgrowth of intermediate monocytes, a type of white blood cell that is useful in short bursts for healing but can drive chronic inflammation and tissue damage if it persists. Specifically, an epoxy-oxylipin known as 12,13-EpOME was found to suppress the p38 MAPK protein signaling pathway, which drives monocytes into their inflammatory state.
To test this in humans, the research team gave healthy volunteers injections of UV-killed E. coli bacteria to trigger a temporary, localized inflammatory response. Participants were divided into two groups. One group received the drug GSK2256294 two hours before inflammation was induced. The other received it four hours after inflammation had already begun.
GSK2256294 works by blocking the enzyme soluble epoxide hydrolase, which normally breaks down epoxy-oxylipins. By blocking this enzyme, researchers sustained higher levels of the protective molecules in the body.
Both groups showed faster pain resolution and a significant reduction in intermediate monocytes in blood and tissue samples. The treatment did not significantly alter outward physical markers like redness or swelling, suggesting it targets deep immune processes rather than surface-level symptoms.
The discovery is significant because it offers a way to restore immune balance rather than broadly suppressing the immune system, which is a common limitation of existing anti-inflammatory drugs. Because GSK2256294 is already considered suitable for human use, the researchers suggest it could be repurposed to treat flares in chronic conditions such as rheumatoid arthritis and cardiovascular disease.
