Scientists at University College London have identified a biological mechanism responsible for shutting down inflammation, according to research published in Nature Communications. The discovery centers on epoxy-oxylipins, small fat-derived molecules that function as natural suppressors of excessive immune activity. These molecules help prevent the overaccumulation of intermediate monocytes, a type of white blood cell that can contribute to chronic inflammation if they persist too long in the body.
To test their findings in humans, researchers administered a drug called GSK2256294 to healthy volunteers who received injections of inactive bacteria. This approach triggered temporary inflammation without causing infection, allowing scientists to observe the inflammatory response in real time. The drug works by blocking soluble epoxide hydrolase, an enzyme that normally breaks down epoxy-oxylipins. By preventing this enzyme from functioning, researchers allowed protective molecules to accumulate in higher concentrations.
Both preventive and therapeutic applications of the drug produced comparable results. Pain resolved more quickly in treated participants, and levels of intermediate monocytes decreased significantly in both blood and tissue samples. Notably, outward symptoms such as redness and swelling remained largely unchanged, suggesting the treatment affected deeper immune processes. Molecular analysis revealed that one specific epoxy-oxylipin, 12,13-EpOME, suppresses a protein signaling pathway called p38 MAPK, which normally drives the transformation of monocytes into their intermediate form.
The findings suggest a fundamentally different approach to treating chronic inflammatory diseases compared to existing therapies. Most current anti-inflammatory treatments work by suppressing immune system activity, which can reduce inflammation but may compromise the body’s ability to fight infection. This newly identified pathway offers an alternative strategy by enhancing a natural process the body already employs to resolve inflammation. Researchers indicate that sEH inhibitors could potentially be used alongside existing medications to treat conditions including rheumatoid arthritis and cardiovascular disease, with clinical trials potentially following this discovery.
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