Newly discovered metabolic mechanism could be an off-switch for inflammation

Newly discovered metabolic mec...
Researchers at Trinity College Dublin may have discovered a way to switch off inflammation
Researchers at Trinity College Dublin may have discovered a way to switch off inflammation
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Researchers at Trinity College Dublin may have discovered a way to switch off inflammation
Researchers at Trinity College Dublin may have discovered a way to switch off inflammation

Researchers at Trinity College Dublin have uncovered a new metabolic process involved in the immune system's inflammatory processes. The discovery suggests manipulating this mechanism could essentially "switch off" inflammation, which the researchers hope could lead to the development of entirely new anti-inflammatory drugs to treat a host of auto-immune disorders.

When the body is working properly, inflammation is a good thing. It is our natural immune system response to help the body protect itself from harmful external stimuli. But sometimes inflammation can flare up out of control and result in a number of diseases, from simple allergies to more complex gastrointestinal disorders. Inflammation has also recently been suspected to be connected to everything from cancer to depression.

The best treatment we have today for an acute inflammatory flare-up is still an old-fashioned steroidal immunosuppressive drug. These drugs can sometimes have significant negative side-effects and stifle the immune system to such a degree that it makes the patient highly susceptible to other infections.

Now a team at Trinity College Dublin has found that "itaconate" – a molecule derived from glucose – may act as an off-switch for macrophages, one of the immune cells responsible for inflammatory responses.

"My lab has been exploring metabolic changes in macrophages for the past six years and we've come across what we think is the most important finding yet," explains LukeO'Neill, joint leader in the research at Trinity. "It is well known that macrophages cause inflammation, but we have just found that they can be coaxed to make a biochemical called itaconate. This functions as an important brake, or off-switch, on the macrophage, cooling the heat of inflammation in a process never before described."

Research into itaconate is very much inits early stages, and while other recent studies have revealed the compound to be an important regulator of macrophage function, very little has been known about how it actually works. This new study offers a vital insight into how macrophages could be manipulated to reduce the levels of inflammation they produce.

"The macrophage takes the nutrient glucose, whose day job it is to provide energy, and surprisingly turns it into itaconate," says Dylan Ryan, joint first author on the new study. "This then blocks production of inflammatory factors, and also protects mice from the lethal inflammation that can occur during infection. We've found that itaconate can directly modify a whole host of proteins important for inflammation in a chemical reaction never before described, and that this reaction is important for the anti-inflammatory effects of itaconate."

The researchers are investigating several pathways for future study. As well as examining how this newly revealed mechanism could play a part in the onset of inflammatory diseases, it hopefully could lead to the development of new anti-inflammatory drugs that could treat everything from inflammatory bowel disease to arthritis.

The study was published in the journal Nature.

Source: Trinity College Dublin

Craig Jennings
Take your shoes off and read a book under a tree. It's free. It'll help right now. It's free. Check out "grounding" at the National Center for Biotechnology Information. It's free. You'll feel like a hippie, but you've read the peer reviewed studies at the NCBI so you're just coming up against how you've been programmed to need medicine. It's free. Inflammation is good.... unless it gets carried away. Did I say grounding was free? Probably why it's not advertised :D
Ralf Biernacki
Take a pinecone. It's free. Take your cap off and tap yourself on the noggin with it. It's free. It doesn't do anything, and you'll look and feel like an idiot, but what matters is that It's free.
Craig Jennings
Not sure why you'd do that Ralf, I suggest something that works that's free and you suggest... performance art? Perhaps the repetition of "free" isn't the obvious, social commentary as I imagined it to be. To the next reader if you feel the need for more performance art, please look up the studies on "Grounding" at the NCBI. That's why you read NewAtlas right?
I am surprised that no mention was made of the fact that heart disease is also closely related to inflammation.
Important work, indeed