Researchers at University College London (UCL) have identified a mechanism that helps the body turn off inflammation, which could inform new treatments for chronic diseases. The study, published in Nature Communications, found that molecules called epoxy-oxylipins act as natural regulators of the immune system by preventing excessive growth of certain immune cells known as intermediate monocytes. These cells are associated with chronic inflammation and related health conditions.
The research involved healthy volunteers who received an injection of UV-killed E. coli bacteria to trigger a controlled inflammatory response. Participants were divided into two groups and given a drug called GSK2256294 at different times. This drug blocks the enzyme soluble epoxide hydrolase (sEH), which normally breaks down epoxy-oxylipins.
Results showed that inhibiting sEH increased levels of epoxy-oxylipins, led to faster pain resolution, and reduced intermediate monocyte levels in both blood and tissue samples. However, there was little change in visible symptoms such as redness or swelling.
Further laboratory tests indicated that one specific epoxy-oxylipin, 12,13-EpOME, suppresses a protein signal known as p38 MAPK that is responsible for transforming monocytes. This effect was also observed when volunteers were given a separate drug that blocks p38 MAPK.
Professor Derek Gilroy from UCL Division of Medicine stated: "This is the first study to map epoxy-oxylipin activity in humans during inflammation." He added: "By boosting these protective fat molecules, we could design safer treatments for diseases driven by chronic inflammation." Professor Gilroy emphasized the relevance to autoimmune diseases and noted the potential for repurposing an existing human-use drug for treating flares in chronic inflammatory conditions.
The team focused on epoxy-oxylipins because previous animal studies suggested their role in reducing inflammation and pain, but their function in humans had not been established until now.
Dr Bracken commented on future directions: "For instance, rheumatoid arthritis is a condition in which the immune system attacks the cells that line your joints. sEH inhibitors could be trialled alongside existing medications to investigate if they can help prevent or slow down joint damage incurred by the condition."
Dr Caroline Aylott from Arthritis UK said: "The pain of arthritis can affect how we move, think, sleep and feel, along with our ability to spend time with loved ones. Pain is incredibly complex and is affected by many different factors. We also know that everybody's pain is different.
"That is why it is important that we invest in research like this, that helps us understand what causes and influences people's experience of pain.
"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."
Funding for this research came from Arthritis UK and included collaboration between researchers at UCL, King's College London, University of Oxford, Queen Mary University of London, and National Institute of Environmental Health Sciences (USA).
