A human study reveals how naturally occurring fat-derived molecules help switch off inflammation.
Researchers at University College London (UCL) have identified an important biological process that helps the body bring inflammation to an end, a finding that may eventually support new treatments for chronic illnesses that affect millions of people worldwide.
Inflammation is the body’s frontline defense against infection and injury. But if this response fails to shut down at the right time, it can contribute to serious conditions, including arthritis, heart disease, and diabetes. Scientists have long known that the immune system must shift from fighting to repairing, yet the signals that guide this transition have not been fully understood.
In a study published in Nature Communications, the team reports that small fat-derived molecules called epoxy-oxylipins can act as natural brakes on immune activity. The researchers found that these molecules help prevent the buildup of a specific immune cell type, intermediate monocytes, which can promote long-lasting inflammation – linked to tissue damage, illness, and disease progression.
Studying Inflammation in Humans
To examine this process in people, the researchers triggered a controlled, temporary inflammatory response in healthy volunteers. Participants received a small injection of UV-killed E. coli bacteria into the forearm, producing a short-lived reaction marked by pain, redness, heat, and swelling – similar to what can occur after infection or injury.
Volunteers were assigned to one of two groups: prophylactic arm and therapeutic arm.
At set time points, participants were given a drug called GSK2256294. The drug blocks an enzyme known as soluble epoxide hydrolase (sEH), which normally breaks down epoxy-oxylipins.
- Prophylactic arm: Participants received the drug two hours before inflammation began to test whether raising epoxy-oxylipins early could limit harmful immune changes. In this group, there were 24 volunteers – 12 were treated, 12 untreated (placebo).
- Therapeutic arm: Participants received the drug four hours after inflammation started, reflecting treatment after symptoms appear. In this group there were 24 volunteers – 12 were treated, 12 untreated (placebo).
In both groups, blocking sEH with GSK2256294 increased epoxy-oxylipin levels, helped pain resolve more quickly, and markedly lowered intermediate monocytes in blood and tissue – the immune cells linked to chronic inflammation and disease. The drug did not significantly change outward signs such as redness and swelling.
Pinpointing the Molecular Mechanism
Further tests revealed that one epoxy-oxylipin, 12,13-EpOME, works by shutting down a protein signal called p38 MAPK, which drives monocyte transformation. This was confirmed in lab experiments and in volunteers given a p38-blocking drug.
First author Dr Olivia Bracken (UCL Department of Aging, Rheumatology and Regenerative Medicine) said: “Our findings reveal a natural pathway that limits harmful immune cell expansion and helps calm inflammation more quickly.
“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.”
Corresponding author Professor Derek Gilroy (UCL Division of Medicine) said: “This is the first study 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 added: “This was an entirely human-based study with direct relevance to autoimmune diseases, as we used a drug already suitable for human use – one that could be repurposed to treat flares in chronic inflammatory conditions, an area currently bereft of effective therapies.”
Why epoxy-oxylipins?
Scientists chose to study epoxy-oxylipins because these fat-derived molecules were known from animal research to reduce inflammation and pain, but their role in humans remained unknown.
Unlike well-studied inflammatory mediators, such as histamine and cytokines, epoxy-oxylipins are part of an underexplored pathway that scientists believed could naturally calm the immune system.
Next steps
The discovery opens the door to clinical trials exploring sEH inhibitors as potential therapies for conditions like rheumatoid arthritis and cardiovascular disease.
Dr Bracken said: “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, Head of Research Delivery at 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, which 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.”
Reference: “Epoxy-oxylipins direct monocyte fate in inflammatory resolution in humans” by Olivia V. Bracken, Parinaaz Jalali, James R. W. Glanville, Larrissa Benvenutti, Emma S. Chambers, Hugh Trahair, Madhur Motwani, Karen T. Feehan, Jamie G. Evans, Jhonatan de Souza Carvalho, Roel P. H. De Maeyer, Arne N. Akbar, Fred B. Lih, Darryl C. Zeldin, David Bishop-Bailey, Matthew L. Edin and Derek W. Gilroy, 16 January 2026, Nature Communications.
DOI: 10.1038/s41467-025-67961-5
The study was funded by Arthritis UK and involved researchers at UCL, King’s College London, University of Oxford, Queen Mary University of London, and National Institute of Environmental Health Sciences, USA.
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33 Comments
Love Jesus with all your soul!
I have Erdheim-Chester Disease. Histiocytes replicate when unnecessary and cause inflammation with ECD. We are always hoping for new treatments. Could drug GSK2256294 help us?
Nonsense. Fix your diet
What are you on about?
“Fix your diet”? This article is about arthritis, not weight loss.
I’ve seen endless claims of fixing various ailments with restrictive eating from people in all diet spheres, and after trying all of them (whole food plant based, keto, paleo, carnivore, long fasts, vegetarian, bio energetic, Mediterranean, 1200 calories a day with nothing artificial, etc), the only thing that stops me from having crippling gout (a form of arthritis) flare-ups, is taking allopurinol and drinking lots of water.
Yeah, fixing your diet is a good way to lose weight, prevent heart disease, prevent diabetes, sleep better, give you more energy, fix your digestion. But for many (maybe most), no diet will fix any form of arthritis.
For gout, try eating min. 6 dark (Bing) cherries daily. It works. My husband had gout. I would come home from work to find him in bed, rocking while holding his great toe because he was in so much pain. The Allopurinal didn’t do much to help him. But when he started eating the dark cherries, his gout pretty much cleared up.
Dark cherry juice maybe helps
Gout and associated issues , was largely from underused or lack of sufficient Vitamin c and minerals such as magnesium, Zinc , and selenium.
There are several forms of concentrated vitamin c , that is beneficial in daily capsule or powder forms..,,Some mixes the fruit based vitamin c powders with a protein powder drink/smoothie….As vitamin c , also helps with inflammation in our body….Also alleviates many skin djsorders….But have to start with smaller amounts such as 1/4 to 1/2 teaspoon , to allow our systems/gut to get use to it….
This is very interesting to me I would love to see how it turns out since I have cerebral palsy and three forms of arthritis if you ever need my help I’d be glad to volunteer🙂 although these results are only preliminary I am excited to see where it goes keep up the good research guys
I would suggest you do a deep dive into wellness and supplemental supplements and vitamins/minerals…..am a 70’s man , with no arthritis or inflammation, and all my joints works well with no pains whatsoever….
But I have experimented with many over the counter enzymes, amino acids , and balanced amounts of vjtamins/minerals….Amino acids are the building blocks of human bodies….Search the Ai Grok , for the proper combinations for you….Most are safe in combinations….but start slower , with smaller amounts for gut health….Also look up benefits of amino acid L-Citrulline for better blood flow….
Amen God is good strong then love has ever been and powerful in healing and can read are hearts instead of our mouths so we don’t lie to him ,we had 1 day since we were born on 6th day on earth ,that’s why we are a child of God .amen he is healing and fresh not speaking for him speaking Abt him,that’s why we pray for man not to them,we pray to our God ,father ,son ,holy ghost,God is greater than ourselves,
Great research finding and I am sure will lead to a lot of relief for people. However I have a question, why are so many people suffering from inflammation, and why does the body overall behave in this manner.? Is there a trigger in our environment or how we live today that is causing this more than would be expected.?
Sugar and yeast/gluten causes inflammation. Since I have stopped eating same, my inflammation levels have dropped significantly
You have not stopped eating “sugar and yeast/gluten.” No diet can eliminate all sugars, as they are the essential molecules on which all energy in your body is generated. What you refer to a “sugar” is only processed cane or beat sugar. What you refer to as yeast/gluten is likely a just a reference to bread, which is actually incredibly good for you not bad for you, and like the many Americans who incorrectly think they have celiac disease based on del-diagnosis, you probably don’t. If you actually understood any of the things you’re talking about it would make sense for you to comment here, but you don’t understand inflammation or diet and yet you regale us with your disinformation-posing-as-knowledge.
The words in BALANCE mean anything 2 you ? Also there are other sweetners , that is better for our systems and inflammatory reactions….As sucrose(sugar cane derived sugar) is most caustic to our systems. Some liken to granular caustic rust to our circulatory systems….Try concentrated Stevie or Monk fruit , fkr much better outcomes….
True….have you tried Stevia as a sugar substitute ?
Your diet
Hope this will be precursor to a solution to treat ulcerative colitis also. God help us.
Brooke goldner diet fixes it
All Sjögren’s patients cannot wait for knowing at least about the drug you used in this resarch🙏
Amen! I just wish they would hurry up as I am nearly 80!!!! It’s very debilitating & depressing having a chronic illness.
Amen! I just wish they would hurry up as I am nearly 80!!!! It’s very debilitating & depressing having a chronic illness.
Lyn…..see my reply below for a possible solution to your gut issues ?
Better still….Look up Dr. William Davis on you tube…..Has much research on gut health and solutions….Few doctors will mention those solutions , as they have drugs 2 push….
Auto immune conditions are strongly linked as comorbids for neurodivergent people. Science seems to be surging forwards at the moment. We wouldn’t be without the neurodivergencev in our family – but for us to have relief from our long list of inflammatory conditions gives us hope!! ♡
Autoimmune doesn’t exist.
What are you talking about G?…
Autoimmune disease is defined as a situation where the immune system’s T cells and B cells attack the body’s own tissues instead of foreign invaders, producing “autoantibodies” and self‑reactive immune cells that cause damage.Scientists recognize more than 80–100 autoimmune diseases, including type 1 diabetes, multiple sclerosis, lupus, rheumatoid arthritis, inflammatory bowel disease, Hashimoto’s thyroiditis, celiac disease, and Sjögren’s syndrome
Arthritis sufferer there is an a product researched in Humanised Mouse Model in 2012 called PS372424 and in liquid form with Cambridge Biosciences UK can be made into Pill form non toxic no side effects no effect on AutoImmune system yet no docs or research teams or medics know any thing or pretend to know anything look info about PS372524 on Google it would be a miracle pill for Inflammatory Diseases l have written o health bodies about PS372424 but as usual with medics fobbed off cos they are lazy minded
I’ve had been dealing with degenerative disc disease for over 30 yrs & 4 yrs ago I was diagnosed with severe nerve damage no circulation at all. Neuropathy causes numbness, tingling, itching, burning mouth syndrome, I’m in constant pain everyday. I’ve been through so many doctors & specialist in many places & no hope what’s so ever. My flare ups are so i extreme it’s ruined my life. No one has any idea to help me nor help me. Inflammation is chronic pain i have to have toradal shots several times a month but that doesn’t help either it honestly makes you want to not be alive cause this pain is too much I take my vitamins, I’ve changed my diet, medications constantly being changed. One Dr after another & no one knows what else to do for me I’ve had several surgeries in my life the osteoarthritis is one thing but nerve damage & neuropathy someone has to be able to help me.
Please what drug working side by side to take the pain RA in my hands arms legs can I safely take not to upset my magnesium I take crystals daily have been hospitalised for this can you forward diet plan
Try the carnivore diet so many amazing results. Check out you tube and decide for yourself.
The government are putting things in our foods and in a our fruit and vegetables. And since we all had coronavirus injections it’s made our immune system weaker and its given is more inflammation. The government doesn’t want us to live longer so they thought ok we’ll contaminate everything we eat. Its strange how we all have some kind of inflammation and illnesses. Look at the old generations who walked every day to get shopping because they had no cars and washed clothes by hand and they still had energy to go out to neighbours houses for chit chat but look at us we can’t do half of the stuff my parents and grandparents did yet we take all sorts of vitamins and minerals yet we still feel aches and pains and have got so much inflammation. These people who are putting chemicals in our foods they think they are God and there playing with our lives. All I can say is karma on them. What goes round comes around back onto them. O don’t know how they sleep at night while nomal people suffer in pain.
More commonly….sucrose in majority of prepared foods/processed foods….has forms of 2 much sucrose sugar( sugar derived from cane sugars) whis is likened 2 rust in our organs and circulatory systems….
I read most comments, and they have nothing to do with this article. I think most do not have an understanding and hear fat they think of diet. I find this study interesting. There is not much that deals with this issue. I have contacted the school and want to know more if there is more. What happens in Europe takes the USA FOREVER to okay it here. The USA has to accept what other countries have done and tested. If it is approved in Europe then we should accept that and let people in the USA have it sooner.