Scientists at University College London have uncovered a natural mechanism that calmly shuts down inflammation once it has done its job. The finding could lead to gentler medicines for conditions such as arthritis, heart disease and diabetes.
Why inflammation must be turned off
Inflammation protects us from infection and injury, but when the response lingers it fuels chronic illnesses. Until now, the exact biological “off switch” remained vague.
Fat‑derived epoxy‑oxylipins act as the brake
The team discovered that tiny fat‑based compounds called epoxy‑oxylipins regulate immune activity. By preventing the buildup of intermediate monocytes – a type of white blood cell linked to prolonged inflammation – these molecules help the body move from attack to recovery.
Human experiment with a controlled wound
Healthy volunteers received a tiny injection of dead E. coli bacteria in the forearm, creating a short‑lived “redness‑pain‑heat‑swelling” episode. Participants were split into a prophylactic group (drug given before inflammation) and a therapeutic group (drug given four hours after symptoms started).
Blocking sEH raises protective lipids
The study drug GSK2256294 blocks an enzyme named soluble epoxide hydrolase (sEH). Inhibiting sEH lets epoxy‑oxylipins accumulate. Both study arms showed faster pain relief and a marked drop in intermediate monocytes in blood and tissue, even though visible redness and swelling changed little.
How the key molecule works
One epoxy‑oxylipin, 12,13‑EpOME, suppresses the p38 MAPK signaling pathway, which normally drives monocyte maturation. Laboratory tests with a p38 blocker confirmed this route.
Implications for chronic disease
Because chronic inflammation underpins many worldwide health problems, targeting the sEH‑epoxy‑oxylipin axis could produce therapies that restore balance without broadly dampening immunity. Researchers envision clinical trials for rheumatoid arthritis and cardiovascular disease.
The work was funded by Arthritis UK and involved experts from UCL, King's College London, Oxford, Queen Mary University of London and the US National Institute of Environmental Health Sciences.