Daijiworld Media Network - London

London, Sep 13: Researchers at University College London (UCL) have identified a biological mechanism that helps the human body switch off inflammation, a discovery that could pave the way for new treatments for chronic inflammatory diseases.

The study, published in Nature Communications, identifies a group of small fat-derived molecules called epoxy-oxylipins that appear to act as natural brakes on the immune system. The molecules help limit the expansion of intermediate monocytes, a type of white blood cell that supports healing in the short term but may contribute to persistent inflammation when present in excessive numbers or remain active for too long.

Inflammation is a vital defence mechanism that helps the body fight infections and repair damaged tissue. However, when it persists, it can damage healthy tissue and contribute to conditions such as arthritis, heart disease and diabetes.

While scientists understand how inflammation begins, how the body determines that a threat has passed and shifts from fighting the threat to repairing tissue has been less clear.

To investigate the process in humans, researchers gave healthy volunteers a small injection of UV-killed E. coli bacteria in the forearm. As the bacteria were no longer alive, they could not cause an infection but were able to trigger a temporary inflammatory response, producing pain, redness, heat and swelling.

The 48 volunteers were divided into prophylactic and therapeutic groups. Researchers administered GSK2256294, a drug that blocks an enzyme called soluble epoxide hydrolase (sEH), at different stages of the inflammatory response.

Under normal conditions, sEH breaks down epoxy-oxylipins. Blocking the enzyme therefore allows higher levels of these protective molecules to remain in the body.

In the prophylactic group, 24 volunteers received the drug two hours before inflammation was triggered, while 12 received the treatment and 12 received a placebo. In the therapeutic group, another 24 volunteers received the drug four hours after inflammation had started, with 12 receiving the drug and 12 receiving a placebo.

Both approaches produced similar results.

Blocking sEH increased epoxy-oxylipin levels, helped pain resolve more quickly and substantially reduced intermediate monocytes in both the blood and tissue. These immune cells have been associated with persistent inflammation and the progression of inflammatory diseases.

However, the treatment did not significantly alter visible signs such as redness or swelling, suggesting that it may have affected deeper immune processes even when outward symptoms remained largely unchanged.

Researchers then examined the molecular mechanism behind the effect. They found that one epoxy-oxylipin, 12,13-EpOME, appears to suppress p38 MAPK, a protein-signalling pathway involved in transforming monocytes into the intermediate form associated with prolonged inflammatory activity.

The mechanism was confirmed through laboratory experiments and in volunteers who received 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.

“Targeting this mechanism could lead to safer treatments that restore immune balance without suppressing overall immunity. With chronic inflammation ranked as a major global health threat, this discovery opens a promising avenue for new therapies,” she said.

Many existing treatments for inflammatory and autoimmune diseases work by suppressing parts of the immune system. While this can reduce inflammation, it can also interfere with the body's ability to fight infections.

The newly identified pathway could offer an alternative approach by strengthening a natural process already used by the body to bring inflammation under control.

Corresponding author Professor Derek Gilroy of UCL’s Division of Medicine said the study was the first to map epoxy-oxylipin activity in humans during inflammation.

“By boosting these protective fat molecules, we could design safer treatments for diseases driven by chronic inflammation,” he said.

Gilroy added that the study was entirely human-based and could have direct relevance to autoimmune diseases because the researchers used a drug already suitable for human use, which could potentially be repurposed to treat flares in chronic inflammatory conditions.

Researchers focused on epoxy-oxylipins because earlier animal studies had indicated that the molecules could reduce inflammation and pain. Their role in humans, however, had remained less understood.

Unlike better-known inflammatory substances such as histamine and cytokines, epoxy-oxylipins are part of a relatively underexplored signalling system. The researchers suspected that the pathway could help the immune system naturally move from an active inflammatory state towards recovery.

The findings could pave the way for clinical trials investigating sEH inhibitors in chronic inflammatory conditions, including rheumatoid arthritis and cardiovascular disease.

Dr Bracken said sEH inhibitors could, for example, be studied alongside existing medicines for rheumatoid arthritis to determine whether they can help prevent or slow joint damage caused by the disease.

Rheumatoid arthritis is an autoimmune condition in which the immune system mistakenly attacks tissue around the joints, causing pain, swelling and stiffness and potentially resulting in long-term damage.

Dr Caroline Aylott, Head of Research Delivery at Arthritis UK, said research into the causes and influences of pain was important because arthritis pain can affect movement, sleep, mental wellbeing and people's ability to spend time with loved ones.

“We are excited to see the results of this study, which has found a natural process that could stop inflammation and pain. We hope in the future that this will lead to new pain management options for people with arthritis,” she said.

Intermediate monocytes are white blood cells involved in fighting infections and repairing tissue. They can help coordinate the immune response and support recovery during short periods of inflammation, but excessive numbers or prolonged activity can keep the immune system switched on and contribute to chronic inflammation.