Inflammasomes - a Primer on Inflammation

May 25, 2015Inflammasomes: a Primer on Inflammation Reference:   World Jr Diabetes, Scientific American May 2015, Diabetes, gout, Alzheimer’s, asbestosis, erectile difficulty, heart attacks all have something in common. They are primarily diseases of inflammation. Yup, inflammation is the problem. (Redness, swelling, pain, warmth) All of these “diseases” share a common pathway. They may affect different organs (fat tissues, liver, joints, brain lung, heart) but they share a common pathway on how the illness comes about.   That changes the way we think about them. Instead of treating the organ, it’s time to start thinking about treating the underlying pathway.   That means we have to understand the underlying pathway. Inflammation. What is inflammation?   Everyone is familiar with “stranger” inflammation. When a bacteria invades your body because you cut your finger, your innate immune system recognizes that it is a stranger, just like a virus, a parasite or a fungus, and your innate system puts out signals that danger is at hand.   Besides “stranger” initiated inflammation, there is also “danger” initiated inflammation. If you crush a cell with trauma, pieces of DNA, or ATP or fatty acids show up in the space between cells where they aren’t normally present. Your guardian immune cells assume that “strangers” must be around for damage to be there, and also set off the initiation of inflammation.   Beta-amyloid in your brain, uric acid in your joints, cholesterol in the wall of your arteries can all the set off the same sequence – without a stranger being there to start it all. See the common pathway? The core concept is that seemingly common things, in the wrong place in your body can also inadvertently set off the fire alarm. For the last decade or so, we thought there was a hopeless maze of signaling that was complex beyond comprehension. Not so. There is a common pathway.   Certain cells called macrophages have the responsibility to eat up “danger” and digest it. They are our body’s garbage trucks.   Here is where it gets interesting. These macrophages respond to broken bits of DNA, or RNA or other DAMPs (Danger associated molecular patterns) with two patterns. One is to initiate the production of danger signals. The other pattern is to assemble a factory to process those signals. That factory is called the inflammasome. The job of the inflammasome is to process the chemical signals of inflammation and activate them. Finally, it ships them out of the cell to call for help and keep the process going.   IL-18 and IL-1β are the two principle signaling molecules. Those two compounds circulate around, increasing blood flow, making tissue swell and all the other processes of what we call inflammation. Now, if you want to sound particularly savvy, you can say the phrase, “I’m going to suppress my NLRP3 inflammasome today.” the next time you are offered a brownie and you really didn’t want the carbs.   The modulation of inflammasomes is the future of medicine.   The NLRP3 inflammasome may be one of the most influential because it is the one in Alzheimer’s that responds to amyloid and goes about killing off brain cells. And why is it important?   Because your can shut it down and turn it off by a chemical called beta-hydroxybutyrate. And what is beta-bydroxybutyrate? It's a ketone body, release by fasting and eating a low carb diet. WWW.   What will work for me?   Hmmm. I can turn off the inflammatory process by fasting? That’s no fun. But a low carb diet is good for me? Yup, this is how it works.   On a low carb diet, your body turns on fat consumption, and that releases the ketone called beta hydroxybutuerate.  And that turns off your inflammasome.   So, practice this phrase with me. “I’m turning off my NLRP3” as a way of giving yourself the willpower to resist that almond extract flavored chocolate chip triple chocolate chewie gluten free brownie sitting in the fridge.   I need the practice, because I had four of them yesterday.   Pop Quiz
  1. Inflammasomes are the factories our bodies make inside of cells that start the process of inflammation. T or F
True
  1. Inflammation is when your tissue gets cold, white, quiet and numb. T or F
False. Red, hot, painful and swollen
  1. Your body can respond to “danger” and “stranger” signals in the same way. T or F
Sounds like you are getting it
  1. The particular inflammsome called NRLP3 can be turned off by fasting. T or F
In a nutshell, that’s it. The ketone body called beta-hydroxybuturate is a ketone body you naturally make when you are digesting and releasing fats – and that turns NLRP3 off
  1. Inflammasome explain how many diseases are caused by the same cellular process – just showing up in different cells and tissues. T or F
Yes – this common pathway gives us reason for much more hope at turning those diseases off.

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