Human Trial Reveals Natural Brake on Inflammation — SkimNews
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- UCL researchers published in Nature Communications that epoxy-oxylipins act as a natural brake on inflammation by preventing intermediate monocytes from accumulating and keeping the immune system active too long.
- GSK2256294, a drug already suitable for human use, was tested in 48 healthy volunteers injected with UV-killed E. coli to trigger inflammation: 24 received the drug two hours before the trigger, 24 four hours after, each with a matched placebo group of 12.
- Blocking soluble epoxide hydrolase raised epoxy-oxylipin levels, accelerated pain resolution, and sharply reduced intermediate monocytes in blood and tissue, though visible redness and swelling showed no significant change.
- 12,13-EpOME appears to suppress the p38 MAPK signaling pathway that drives monocytes into the pro-inflammatory intermediate form, a mechanism confirmed in lab experiments and with a direct p38 blocker.
- First author Dr. Olivia Bracken said targeting this pathway offers safer treatments that restore immune balance without suppressing overall immunity.
- Corresponding author Professor Derek Gilroy said GSK2256294 could be repurposed for chronic inflammatory flares, calling this the first study to map epoxy-oxylipin activity in humans during inflammation.
- Funded by Arthritis UK, the study involved UCL, King's College London, University of Oxford, Queen Mary University of London, and the U.S. National Institute of Environmental Health Sciences, with clinical trials in rheumatoid arthritis and cardiovascular disease planned as the next step.
Why it matters: Existing anti-inflammatory drugs suppress immunity broadly, interfering with the body's ability to defend itself; this UCL study maps a natural shutdown pathway that instead boosts the body's own brake, using GSK2256294 — already approved for human use — as a candidate for clinical trials in rheumatoid arthritis and cardiovascular disease.
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