Researchers at University College London (UCL) have discovered a natural mechanism within the immune system that helps to switch off inflammation. This finding could lead to new treatments for chronic inflammatory diseases. The study identified a group of fat-derived molecules, called epoxy-oxylipins, as key components in this shutdown process.
Epoxy-oxylipins act as natural brakes on the immune system. They help to prevent the excessive growth of intermediate monocytes, a type of white blood cell. While these cells support healing in the short term, their prolonged accumulation can contribute to chronic inflammation. Understanding how the body naturally resolves inflammation has been less clear than understanding its initiation.
To investigate this process in humans, researchers injected healthy volunteers with UV-killed *E. coli* bacteria. This triggered a temporary inflammatory response without causing infection. Participants received a drug, GSK2256294, which blocks an enzyme that breaks down epoxy-oxylipins. This allowed more of these protective molecules to remain in the body. The drug was administered either before inflammation began or after it started.
Both administration methods yielded similar results. Blocking the enzyme increased epoxy-oxylipin levels, which led to faster pain relief and a significant reduction in intermediate monocytes in both blood and tissue. These immune cells are linked to persistent inflammation. The treatment did not visibly reduce redness or swelling, suggesting it affected deeper immune processes. Further investigation revealed that one epoxy-oxylipin, 12,13-EpOME, suppresses a protein signaling pathway (p38 MAPK) that drives monocyte transformation into the intermediate form.
This discovery offers a potential new strategy for treating inflammatory conditions. Current treatments often suppress the immune system, which can compromise the body's defenses. By contrast, this new approach aims to strengthen the body's natural inflammation-resolving processes. This human-based study used a drug already suitable for human use, suggesting it could be repurposed for chronic inflammatory conditions.
The findings pave the way for clinical trials of soluble epoxide hydrolase (sEH) inhibitors in conditions such as rheumatoid arthritis and cardiovascular disease. Researchers believe these inhibitors could potentially be used alongside existing medications to prevent or slow joint damage in autoimmune diseases.
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