The immune system is a powerful, necessary shield that has to spring into action when an infection has to be eliminated or an injury must be repaired. But it must also be kept under control. When immunity and inflammation goes awry, they can lead to allergies, chronic autoimmune disease, sepsis, and other problems. Scientists are still learning about how immune system activity is properly maintained and controlled. A new study reported in Nature Communications has shown that there are small molecules derived from fats that can help tamp down immune activity. These molecules are called epoxy-oxylipins, and they can stop immune cells known as intermediate monocytes from proliferating excessively. These cells have previously been linked to diseases and tissue damage.
In this study, volunteers were injected in their forearms with a small amount of E. coli bacteria that had been inactivated with UV light, then put in one of two groups. One group was given a drug that blocks an enzyme called soluble epoxide hydrolase (sEH) that degrades epoxy-oxylipins naturally; while the other group got a placebo. The E. coli injection triggered inflammation: itching, pain, redness, and swelling, to mimic what happens after an injury or infection.
The drug, GSK2256294, was being tested for its ability to stop inflammation, since it works to stop the actions of sEH.
This study showed that GSK2256294 increases epoxy-oxylipin levels, and significantly reduced the amount of the inflammation-linked immune cells: intermediate monocytes in blood and tissue. External symptoms like redness and swelling were not affected by the drug.
“Our findings reveal a natural pathway that limits harmful immune cell expansion and helps calm inflammation more quickly,” said first study author Dr. Olivia Bracken of University College London (UCL). “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.”
“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,” added corresponding study author Professor Derek Gilroy of the UCL Division of Medicine. “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.”
More work will be needed before sEH inhibitors can be used to treat inflammatory conditions like rheumatoid arthritis and cardiovascular disease, but this study has opened the door to exploring those options.