Immune 'off switch' identified that could lead to new anti-inflammatory treatments

Researchers at UCL identified a group of fat-derived molecules called epoxy-oxylipins that act as a natural brake on the immune system, preventing excessive accumulation of intermediate monocytes. In a human experiment, boosting this pathway reduced inflammation-related immune changes and sped up pain relief. This could lead to new treatments for chronic inflammatory diseases.

The study employed a controlled human model where UV-killed E. coli bacteria were injected into volunteers' forearms, safely triggering a temporary inflammatory response without causing infection. The experimental drug GSK2256294 works by inhibiting soluble epoxide hydrolase, the enzyme responsible for degrading epoxy-oxylipins, thereby allowing these protective molecules to accumulate in greater quantities.

Both dosing strategies—one administered before inflammation began and another four hours after onset—produced comparable outcomes. While visible symptoms like swelling and redness remained largely unchanged, deeper immune markers shifted significantly. The marked reduction in intermediate monocytes is particularly notable, as these cells have been linked to persistent inflammation and disease progression, suggesting this pathway may hold relevance beyond acute responses. The findings were published in Nature Communications.