Scientists Discover a Hidden Switch That Shuts Down Inflammation

Researchers at University College London (UCL) have identified a biological mechanism that helps the body bring inflammation to an end, a finding published in Nature Communications that could eventually lead to new treatments for chronic inflammatory diseases. Inflammation helps the body fight infection and repair damaged tissue, but if it stays active too long it can harm healthy tissue and contribute to conditions such as arthritis, heart disease and diabetes.

The study points to a group of small, fat-derived molecules called epoxy-oxylipins as part of the process that switches inflammation off. According to the researchers, these molecules act like natural brakes on the immune system, limiting the excessive growth of intermediate monocytes -- a type of white blood cell that supports healing in the short term but can contribute to chronic inflammation if too many build up or remain active for too long.

To study the process in people, the researchers injected healthy volunteers in the forearm with UV-killed E. coli bacteria, which cannot cause infection but still trigger a temporary inflammatory response with pain, redness, heat and swelling. Volunteers were split into a prophylactic arm (given the drug GSK2256294 two hours before inflammation began, 12 treated and 12 on placebo) and a therapeutic arm (given it four hours after inflammation started, also 12 treated and 12 on placebo). The drug blocks an enzyme called soluble epoxide hydrolase (sEH), which normally breaks down epoxy-oxylipins, so blocking it lets more of the protective molecules build up.

Both approaches raised epoxy-oxylipin levels, helped pain resolve more quickly and sharply reduced the number of intermediate monocytes in blood and tissue, though outward signs such as redness and swelling did not change significantly. At the molecular level, the researchers found that one epoxy-oxylipin, called 12,13-EpOME, appears to suppress a signalling pathway called p38 MAPK that helps drive monocytes into the inflammation-prolonging intermediate form; they confirmed this both in laboratory experiments and in volunteers given a drug that directly blocks p38.

"Our findings reveal a natural pathway that limits harmful immune cell expansion and helps calm inflammation more quickly," said first author Dr. Olivia Bracken of UCL's Department of Ageing, Rheumatology and Regenerative Medicine.

Corresponding author Professor Derek Gilroy of UCL's Division of Medicine said the findings could pave the way for clinical trials testing sEH inhibitors in conditions such as rheumatoid arthritis and cardiovascular disease.