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And team of researchers from University College London has discovered a key mechanism that helps the body deactivate inflammation, an advance that opens the door to new treatments for autoimmune diseases that affect millions of people. Their conclusions appear collected this Friday in Nature Communications.
Inflammation is the body’s first line of defense against infections and injuries, but when not properly deactivated, it can lead to serious conditions such as arthritis, diabetes, or many others.
The mechanism by which the body decides to stop its immune response, or make it less disproportionate, and begin healing has been a mystery to science.
body fat molecules
Now, this study reveals that tiny molecules derived from body fat called epoxyoxylipins act as natural brakes on the immune system, preventing the excessive growth of certain immune cells, known as intermediate monocytes, that can cause chronic inflammation.
To test their thesis, the researchers gave healthy human volunteers a small injection of already dead ‘Escherichia coli’ bacteria in the forearm, which triggered a short-lived inflammatory reaction (pain, redness, heat and swelling) similar to that which occurs after an infection or injury.
The volunteers were divided into two groups: the prophylactic group and the therapeutic group. Both groups were given at various times a drug called GSK2256294, which blocks an enzyme known as soluble epoxide hydrolase (sEH), which naturally breaks down epoxyoxylipins.
The 24 participants in the prophylactic group (12 were treated and 12 were placebo) received the drug two hours before inflammation began, to see if increasing epoxyoxylipins early could prevent harmful immune changes.
The 24 participants in the therapeutic group (half treated, half placebo) received the drug four hours after the onset of inflammation, mimicking the real treatment once symptoms appear.
In both groups, it was seen that (sEH) blockade increased the levels of epoxyoxylipins, accelerated the resolution of pain and drastically reduced the levels of intermediate monocytes in the blood and tissues, that is, immune cells related to chronic inflammation and disease.
Interestingly, the drug did not significantly alter external symptoms, such as redness and/or swelling.
Additional testing revealed that an epoxyoxylipin (12,13-EpOME) acts by deactivating a protein signal called p38 MAPK, which drives the transformation of intermediate monocytes. This was confirmed in laboratory experiments and in volunteers who were given a p38-blocking drug.
“Our findings reveal a natural pathway that limits the harmful expansion of immune cells and helps calm inflammation more quickly,” says one of the authors, researcher Olivia Bracken, from University College London, in a statement from the center.
“Focusing on this mechanism could lead to safer treatments that restore immune balance without suppressing general immunity as is the case with current treatments. This discovery opens a promising avenue for new therapies,” he adds.
EFE
