Chronic and Systemic Inflammation

If I’m reading this correctly, there is no bright line between acute and chronic inflammation.  Chronic inflammation is acute inflammation that didn’t go away.  Over time this may lead to accumulated effects, and the distribution of mediators and their sources may shift, but there’s a lot overlap.

There’s a few ways chronic inflammation can hurt you.  One is that is releases immune cells (aka white blood cells)  into your tissues.  Didn’t I list that as one of the features of inflammation last time?  Yes, yes I did.  When you have an infection in the tissue, you want immune cells there to go after it.  But if letting immune cells run around organ tissue didn’t have any side effects, we’d do it all the time.    Immune cells are very very good at distinguishing foreign body from host , but not perfect.  The more time they spend in the trenches, the more likely they are to misidentify a host protein as dangerous and attack.  In the worst case this triggers a really ugly autoimmune disorder.  In a milder case it triggers more inflammation.   I think you can see where this is going. So much like being in a hospital or on crutches, you want your immune cells to be circulating in tissue for as long as you need, but no longer.

Similarly, some of the proteins released during inflammation (aka positive acute-phase proteins), which do useful things like signal inflammation, coagulate blood, or retard microbial growth, can change shape* and become insoluble.  These form fibrous  masses in intracellular space known as amyloids.  Amyloids are or are associated with some of our most terrifying diseases, like Alzheimers and Mad Cow Disease, and the amyloids from inflammation can contribute to these, although they’re not necessarily the most important part.

Chronic inflammation can be self-reinforcing in other ways.  Swelling is just about the least useful reaction to an ingrown toenail, but it’s what we do.

Everything I’ve talked about so far has been local inflammation, where the reaction is contained to one identified area.  There is also systemic inflammation, in which the vasodilation is body-wide.  It’s associated with all sorts of bad things, including overeating and obesity, which immediately makes me think we don’t know the real issue because both those topics are moral panics in our society.

*Quick lesson in proteins.  Proteins are made of up a long string of amino acids.  The order of amino acids is called the primary structure.  Individual bits of those string fold themselves into 3-d structures such as the ß-Hairpin and  Greek Key.  Those structures, also known as motifs, make up the secondary structures.  The motifs in turn interact to form the total three dimensional shape of the protein, which is the tertiary structure.  The tertiary structure is determined by the electrical charges and physical shape of the primary structure.

In general, a given primary structure has a single tertiary structure, because there’s only one island of stability.  However it is possible for a second island to exist, and the protein to convert to it- either it’s more stable in a new environment, or something catalyzed the reaction and it can’t go back.  Very, very rarely, this new tertiary structure is capable of catalyzing other proteins of the same type to its new shape.  These are known as prions (e.g. Mad Cow Disease) and they awesome and terrible.