What is Inflammation?

This is a word that gets thrown around a lot, but what does it mean, actually. Here we ask Dr. House, as it were.


Question:

Dear Dr. House. What is inflammation?

Answer:

Deep in the jungles of Java, is a mysterious species of animal which manufactures acid as a defense against just about everything. We call this species, “Man”, although actually we should call it “Man and Woman”. You know, Homo Sapiens, the link that all the missing links supposedly hooked UP to, once they got tired of the sun beating down on the African Rift Valley and got rid of most of the hair that was REALLY, REALLY, HOT, and not very attractive either or at least did not photograph well. Inflammation was not just a warning to humans, it was a stiff dose of acid for whatever predator tried to get inside us. Ninety percent of the life threatening organisms are microscopic bugs, so we needed this acid to polish them off. For lions and tigers, we could just mess with their habitat, which used to mean hiding so they couldn’t find us, but now means something else entirely.

This was back when primates discovered that heaving feces and biting might not be the very best way to kill, so they evolved to develop better methods (unless you include the Jerry Springer show, where they prove evolution never succeeded as an experiment of Nature).

Not that I am sold on the whole story as given, since medical statistics show a clear and ongoing DE-evolution in the gene pool. For example, sperm counts are down from four hundred million to the sissy level of about 20 million, and the SAT scores have declined predictably for years, six percent in the last year alone. Fifty percent of the population now gets diabetes as opposed to 5% in 1920. Our genome equals the distance to the moon and since we know how long it takes an enzyme to evolve, it would have taken longer than the universe has been around to “evolve” what is in us.

Still, I do like monkeys, and the profession of teaching evolution, while omitting the totally inconsistent facts about complex gene libraries in the simplest of blue green algae, which were the earliest life forms, probably ranks above “adult roles” as a major. It gives jobs to thousands of guys who didn’t make it into medical school so why not. Actually, evolution cannot be supported scientifically, since the DNA of Humans is 97% the same as apes, while our behavior is 100% the same. Any idiot can see there is a problem there.

In the good old days of medical school, “inflammation” was a word that could just be mentioned, without ever explaining the meaning. From very ancient texts, inflammation was sort of a reversely defined word. The primal physicians (one step up from an HMO) used the word to describe four symptoms or signs, which were “Calor (heat), Rubor (redness), Tumor (swelling), and Dolor (pain)”.

Of course this was a superficial definition, which is to say calor, rubor, dolor, and tumor have to do with SKIN, which is a superficial organ, in fact the MOST superficial organ, at least in the majority of us. (Newton’s third law of conversation according to Hugh Laurie, is that for every statement there is an equal and opposite statement, on which an argument can be based). We throw that qualifier in about superficial, just to cut down on crank letters to the editor on things that can prolapse OUTSIDE the body, where you tell us how much better you know neuroscience than we do. Guess again!

Now the problem is that inflammation is not polite enough to confine itself to the skin, which is where its definition makes clear it should remain, if it had any respect and followed the rules of Good Grammar. No indeed. Inflammation goes right through us, right through the flesh, even into our blood vessels (time for a heart attack) and is even found in the brain, of all places (Duh! in central pain).

But wait a minute, maybe one of those four parts forgets to make its appearance for internal inflammation. In fact, no one seems to have seen the brain turn red, even if it is “inflammed”. Call us picky, but if those four don’t really explain inflammation, then what does? Does the brain really turn red in central pain but we miss it? If it does turn red, does it stay that way? SOMETHING is wrong with the definition. Maybe there is something more elementary, more basic to the definition.

Spoiling the simplicity of it all was knowledge discovered in the late sixties about cells which are part of inflammation, the white cells. Although there are about a jillion different types, they may be classified reasonably honestly into a fairly small number. If you have no honesty at all, you can just call them “immune cells”.

Mainly, white cells are either large polymorphonuclear leukocytes, aka neutral granulocytes, or they are lymphocytes, which can be small or large (mostly small). The big granulocytes are for bacteria. They have little packets of very nasty stuff called lysozyme (ie. the enzyme which will eat your face), which they spit on bacteria they have ingested in order to kill them. They also do much of the legwork in making antibodies.

The smaller white cells, the lympocytes, are mainly for viruses. (Yes, Martha, even the newly discovered megagigantic Mimivirus) Mostly, they are B cells or T cells which respond to antigens, which are noteworthy proteins which make something identifiable as “nonself” and therefore worth dissolving (Message to white cells: If the antigen is part of me, leave it alone, if you please; otherwise, KILL, KILL, KILL!!). Doctors were mistakenly taught that viral antigens are incidental proteins which our immune systems can recognize and make antibodies against. Now, we know it is the other way around. Antigens are protein structures sticking out of the viral (or whatever) surface which actually seek out a place to attach to our cells. They are shaped liked keys to fit into our cell membanes, right where they belong. So immunity is really a two way wrestling match, where the viruses win rounds one and two, and then usually we pin them in round three. (Except for AIDS, ebola, lhassa, HPLV, etc)

No one is exactly sure how small lymphocytes kill viruses, or else they would know how to cure AIDS, but they just do. It has something to do with spotting antigens, an immune reaction, and with our topic for the day, INFLAMMATION. If you don’t have enough of inflammation, something will kill you, and if you have too much, you will wish it had killed you.

There are some other oddball “white” cells, such as eosinophils for allergy, and macrophages/mast cells (huge things that are…that are…well generally associated with inflammation, including neuroinflammation). Not to be forgotten are basophils, which just to go along with the crowd, “initiate the processes of inflammation”.

Last of all we come to the glia, which surround neurons, which used to be called “supportive cells” by Dr. Frankensteins who had no idea what glia actually were doing there. We now know that glia perform no structural role whatsoever and therefore cannot be “supportive”. The latest word is that these cells are involved in inflammation, neuroinflammation to be specific. They spit out materials too, such as growth factors, which cause the genes of pain neurons to go postal (hog wild) and take over the protein factories in the genes which make acids.

In retrospect, ALL the inflammatory cells have to do with acid, whether it is the glia or the big neutrophils or other granulocytes which have their toxic granules of lysozymes, which engulf bacteria in acidic toxins, which are so potent that they can actually harm us if too many of them kill and release their enzymes at once.

Rampant infection with bacteria which release their toxins, accompanied by rampant lysozyme activity (our own toxins) is known as “toxic shock”, which is a form of inflammation you don’t want to have, although preferable to central pain.

Inflammation is not necessarily infectious. Scratch your arm with a needle and you will see nearly immediate, tumor, rubor, dolor, and calor in that local area. Inflammation can also occur from chemicals or irritants, as in asthma. Think of infection then as inflammation plus microorganisms.

So having made that vague enough to meet the current state of knowledge, let us focus more on the brain. It is perhaps clearest to consider brain inflammation as anything which produces acids locally. “If the pH drops, the synapse hops”, as Johnny Cochran put it. We made that up. What Johnny actually said was, “If the acid spits, the synapse has fits”.

We could have bypassed all this and just said that acids in the perineural area constitute neuroinflammation or hypersensitization, but you must remember Newton’s Third Law of Conversation. Some smart aleck immunologist would have found something he wants to call inflammation which doesn’t have acid, and then we would have had to research how histamine and bradykinin, plus cytokines like interleukin-1-beta eventually DO feed back to cause acids, but trust us, you don’t want to cross an immunologist. Quicker than you can say “T cell” they will reply in words so confusing that they show just how far away they really are from an AIDS vaccine.

Since we hear no objection from any neurologists, who rarely worry about pain anyway, we think we are safe with the inflammation equals acidity proposition. It is simple, and quite possibly mostly correct.

Now, these acids do not feel good to pain nerves. To be more specific, (the nerve actually being incapable of feeling good or bad), the acids do not feel good to the cortex, remembering that the thalamus teaches the cortex everything it knows.

From a prior article, you know that the thalamus is saturated with acids in central pain, so you know the thalamus is not a happy camper, sitting there behind your eyeballs and visual tracts, with no good way to get rid of the d______ acids which keep wetting it. The thalamus is very angry to be inflammed and so it tries to convince the cortex to do something about it, take some action, but in central pain, this is not possible, because the pathway back down to the cord, by which the brain normally inhibits inappropriate pain (if there is such a thing, maybe in shark bites or the like) cannot get into the dorsal horn of the cord, because the nerves going downward, the “efferents”, meet a bridge which has been taken out. No inhibition is possible because the nerves are cut. We sometimes speak of central pain as “de-afferented” pain because signal cannot get up, but of course the cut also destroys the efferent feedback loop going down.

Even in injured nerves which are not cut, the lack of a chloride carrier makes the cell incapable of firing an inhibitory signal (See KCC2 using SEARCH, for more on this from Jeffrey Coull;. Coull is a leading man on what is making us burn at this very moment). Making things worse for inhibition, BDNF from the glia also blocks the action of GABA, the pain inhibitory chemical of the central nervous system. (See BDNF using SEARCH, at this site).

Now we are quite aware that we have not yet told you what inflammation is, but that is only because no one has ever told us. The real definition is possibly buried somewhere in the Da Vinci code, but medical Illuminati talk about it academically all the time, just the same.

If you are the easily satisfied type you will go along with the tumor, rubor, dolor, calor, thing (if for no other reason, because it is in Latin) but if you are one of the snotty geniuses with a PhD in biochemistry, you will ask the very rude and pertinent question of which chemicals CAUSE each of the four things. We are ready with an answer for you, it is ACIDS.

There you have it, acids all the way. Trust us on this because central pain feels exactly like acid, just under our skin AND the proteomics columns all reveal acids in the dorsal root ganglion and dorsal horn when the pain system is hypersensitized. You can sample the acid feeling for yourself with a little Sub-Q capsaicin. But take our word for it, acids reek and are no fun, and they are also not “God’s will” and, in most importantly, NOT imaginary. Before you mention exceptions, painless soldiers DO actually get pain too, it is just not timed well with the bullet. When it does finally hit, the pain is because of acids. Do NOT try to talk us out of this ACID thing. If you do, we will bore you with a big technical discussion of the acid sensitive ion channels on the near side of the synapse, the ASICs which are part of all pain.

If you want to know which acids, you must go back through this very long site and read all the articles, most of which have to do with pain and therefore will take several lifetimes to read, unless you have central pain in which case the attempts to describe what acids feel like will make you worry your doctor has no idea what you have been saying to her. We will just tease you and say it is the fatty acids and the pre-prostanoid acids, (eicosanoic scids to you PhD’s) but hey, we want you to work for your information and not feed it to you with a silver spoon.

Beside all of this, CP makes our muscles burn, so it hurts to type this. You will have to do a little of the work on your own, and while you are at it, if you don’t mind, would you please send us an email on how to STOP the acids. Thank you kindly, and in case you are curious, placebos don’t do a flipping think for Central Pain. Too much ACID!!!; or if you prefer, “inflammation”.

Yes, I do limp and am addicted to Vicodin because of pain. I’m still right. (Rumor is, House is to be cured of his pain. The public can relate to him better that way–you will all understand this perfectly).