Why Does Inflammation Seem to Underlie All Sickness?

Why Does Inflammation Seem to Underlie All Sickness?
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But the idea was that inflammation, for example cholesterol is transporting energy to any place where it's needed. If you have a cut the body activates inflammation and the cholesterol is taking fat and protein to the place where it's needed.

This Cell Danger Response is thought to be responsible for some large amount of the “harmful” inflammatory response in our bodies. It is being suggested as a cause for syndromes as widely-ranging as metabolic syndrome and autistic spectrum disorders. (Not because it seems like a neat fit; but rather, because experiments to fix/disable CDR in tissues seem to ameliorate the symptoms of this cornucopia of syndromes/disorders!)

The Cell Danger Response is “selfish” because it protects the cell itself from onslaught, but it hinders higher-level functions of the body from eliminating the problem that is causing the cell to react in the first place. The CDR is a bit like when people run screaming to the exits of a building when a fire breaks out: an individually-useful strategy if you don’t know the context you’re in, maybe, but very suboptimal from a bird’s eye view of people being jammed together and trampled upon.

The CDR is very much the way you’d expect cells to react to threat if they were independent unicellular organisms within a colony, rather than cells in a multicellular organism. And, given what we know of the evolutionary history of multicellular life, we might very well have some highly-conserved DNA coding for organism-level responses by individual cells, retained from an era when our cells were their own organisms.

The important thing to realize is that these responses aren’t what the body “wants” in a global sense. They’re optimal for the cells in some game-theoretic way, maybe, but—given that you have a nervous system, and an immune system, and a few other things that all link up to let your body know where damage is and send a lot of just the right type of cell there to fix or fight that damage—the CDR is more harmful than it is helpful. Our immune systems don’t complement it; they obviate it, and its lingering presence actively impedes the immune system’s work. The immune system has its own methods of triggering tissue inflammation, entirely separate from the CDR, and it only deploys these when there’s a global, top-down reason to do so.

Picture our immune system as security in a mall, trying to get people to file orderly out of the mall during a fire, and you won’t be far off. Their job would be a lot easier—and more successful!—if the people didn’t freak out and run randomly away from the fire, but instead just kept about their business apart from following announcements to head toward specific areas of refuge at a measured pace. And while this “human danger response” might be a bad trigger of an otherwise-sensible response to fear, that is useful in more situations than not, the CDR is—as far as we know—useless and counterproductive in 100% of the kinds of dangerous situations cells will encounter in the context of a multicellular organism. (Okay, the CDR might be advantageous outside the body, like if you’re a spermatozoa or spore. It also might be advantageous if you’re a [live] cell in direct contact with the environment, without dead tissue or mucous in the way. But that’s actually really rare in higher animals!)

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And that’s just the least useful inflammatory response our bodies have. We also have a bodily-level whole-immune-system response to suspected parasitic onslaught, that’s pretty counterproductive now that we have a super-bodily-level response to parasites involving bathrooms and hand-washing and food-washing and anti-parasitic drugs.

The parasite immune response serves as a useful contrast to the CDR: while the parasite immune response would become helpful again in the event of a cataclysm that sent humans back to the Stone Age, the CDR would still be counterproductive for us even then. The CDR would only “become useful” for human cells that regress all the way back to being unicellular life-forms. (Sort of like the HeLa cancer cell line.)