UCL Study Identifies Natural Inflammation Brake in Humans — SkimNews
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- UCL researchers identified epoxy-oxylipins — fat-derived molecules that act as a natural brake on inflammation by preventing intermediate monocytes from accumulating and prolonging the immune response, according to a study in Nature Communications.
- GSK2256294, a drug that blocks the enzyme soluble epoxide hydrolase (sEH), was given to 48 healthy volunteers (12 treated and 12 placebo per arm) whose inflammation was triggered by UV-killed E. coli injections in the forearm.
- Both prophylactic dosing (two hours before) and therapeutic dosing (four hours after) inflammation onset produced similar results: faster pain resolution and a sharp drop in intermediate monocytes in blood and tissue, though outward redness and swelling did not significantly change.
- Molecular mechanism: the epoxy-oxylipin 12,13-EpOME suppresses the p38 MAPK signaling pathway, blocking monocytes from transforming into the intermediate form linked to chronic inflammation — confirmed in lab experiments and with a direct p38 inhibitor.
- First author Dr. Olivia Bracken called the discovery a natural pathway that limits harmful immune cell expansion; corresponding author Prof. Derek Gilroy said it is the first study to map epoxy-oxylipin activity in humans during inflammation.
- Arthritis UK's Dr. Caroline Aylott welcomed the findings on pain, and researchers said next steps include clinical trials testing sEH inhibitors in rheumatoid arthritis and cardiovascular disease — conditions where current treatments broadly suppress immunity.
Why it matters: The trial used GSK2256294, a drug already suitable for human use, meaning sEH inhibitors could be repurposed rather than developed from scratch — a faster path to trials in rheumatoid arthritis and cardiovascular disease, where the millions of patients affected by chronic inflammation currently rely on broadly immunosuppressive drugs that compromise the body's ability to defend itself.
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