Why Does Inflammation Seem to Underlie All Sickness? | Hacker News Reader

Why Does Inflammation Seem to Underlie All Sickness?

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287 pointsimartin2k80 comments

Not all inflammation is bad. Supercompensation can't happen without it. In fact, taking anti-inflammatory substances during training can reduce the efficacy of training[0].

[0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023714/

Thanks I’ve actually wondered about this for sometime!

It depends, there are several different form of inflammation. Curcumin seems to have little effect on muscle growth post exercise.

Do you happen to have a source for this? I've been avoiding turmeric after lifting for this very reason.

Would this include foods that are naturally anti-inflammatory? Or are those minor in normal/healthy amounts and thus not detrimental to training?

I see a reference to cancer below, I recently started looking into this, it's actually fascination.

There is actually some research being done on non steroidal anti inflammatory drugs such as celecoxib or diclofenac for treatment of leukemia.

Since Leukemia is actually related to an increase of white blood cells which are produced in response to inflammation/infection I was curious if there's any relationship and immediately found articles such as the following one:

"Celecoxib suppresses autophagy and enhances cytotoxicity of imatinib in imatinib-resistant chronic myeloid leukemia cells"

There's also a bunch of initial research on herbal medicinal herbs and their effect on certain cancer cells. And a lot of them actually were used for their anti-inflammatory properties.

(Personal matter related to a case I have in the family)

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029099/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720497/

[3] https://www.sciencedirect.com/science/article/pii/S002364380...

It is important to look at the overall body of research available on the matter.

What you have linked has no placebo-arm to compare to. In addition, only cells from 6 patients were tested. Furthermore, this is for extremely resistant CML patients who do not respond to imatinib (first line treatment).

However, the introduction of second generation TKI inhibitors is now the standard of care in imatinib resistant CML patients.

I haven’t referenced any particular pubmed entries since there are 6 or 7 second gen TKI’s, however, this reference by the American cancer society gives a good summary of available options.

[1] https://www.cancer.org/cancer/chronic-myeloid-leukemia/treat...

Also, https://www.theguardian.com/science/2018/dec/30/children-leu...

Article is lacking in substance. It's conclusion is basically that there are two types of inflammation - one designed to attack parasites (worms, etc.) the other to attack bacteria and viruses.

The theory it proposes is that because humans have basically eradicated parasitic infections, that part of the body becomes over active and leads to autoimmune disorders.

0 link to sources. I've never heard of this "dual inflammation system". Not saying it's false, just saying, show me the research. Further, show the research that somehow links the under-activity of one to full blown autoimmune disorders. Seems like a weak link.

This is all pretty standard textbook immunology. Providing sources would be a bit like citing Newton when mentioning gravity.

In the innate (first responder) system, inflammation is used as a first line of defense (which can also be detrimental), but the mechanism used depends on the target. White blood cells called eosinophils largely respond to macroparasites like worms (although they also play a secondary role in viral infection). Bacteria and fungi are largely dealt with a different cell type, neutrophils, and virus infected cells by natural killer (NK) cells.

https://en.wikipedia.org/wiki/Eosinophil https://en.wikipedia.org/wiki/Neutrophil https://en.wikipedia.org/wiki/Natural_killer_cell

Not just what the other reply said (standard immunology), this proposed theory itself is fairly standard - most immunologists would at least agree that our immune system is whack because we've eliminated parasites; they'll disagree only on the degree of importance of this particular fadotr

To reinforce the other repliers; people including doctors have deliberately infested themselves with hookworms to combat allergies.

See https://en.wikipedia.org/wiki/Helminthic_therapy

> Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hookworms, whipworms, and threadworms that have evolved to live within a host organism on which they rely for nutrients.

>It's conclusion is basically that there are two types of inflammation - one designed to attack parasites (worms, etc.) the other to attack bacteria and viruses.

No, the article doesn't say that. It says there are many types of inflamation, it mentions several types of inflammation including in response to injury,and also autoimmune diseases, and it ends with a discussion of the possibility one of the many reasons inflammation goes wrong today is an imbalance between two particular types.

I'm just saying that the way the article is written, it comes off as similar to 16th century theory of imbalance of humors [1].

It's just a very surface level explanation, lacking in substance as I said. There's something more concrete going on and this article didn't even attempt to illuminate it.

[1] https://en.wikipedia.org/wiki/Humorism

Interesting to learn that inflammation is just like saying cancer. While the different types share the same base descriptor, they can be entirely different things.

Oddly so is the word fish there is no ocean creature that is a "fish" each is vastly different. It would be like referring to everything not in the ocean by a single name like "terreseta". Even though a camel and a snake are vastly different.

It's perfectly intuitive to me. Taking things further, anxiety could be seen as inflammation of the mind and social unrest as inflammation of a society. Each, in the right amount, serves as an important corrective mechanism for dealing with threats. But in excess, each becomes a gradually destructive force.

Anxiety and physical inflammation are even directly correlated, and social unrest and anxiety probably are too.

Anxiety looks to me more like an allergy of the mind: a useful survival system that does not have much to do in our safe environment and overreacts on perceived threats which are actually harmless.

Yeah I don't know that sounds entirely too logical.

Because it’s not. It tries to make biological truth out of an analogy.

I have a remissive disease that I've only had a few flare ups in my life, all took a few months to get through and all triggered by highly stressful points in my life. Luckily my docs figured it out and prescribed medicine and I haven't had one since, but there is very much a tie between the immune (and inflammation) system and the mind. I don't think it's as mystical as the hippie crystal pushers claim, but it is most definitely there.

The article does not really support the implicit thesis from the title - it lists some diseases that are caused by bad inflamation, some items are maybe surprising - but it does not mention diseases that obviously have different causes like infections. Overall clickbait with no content.

Even in infections, it can be the inflammatory response which causes the damage. I had myocarditis following a flu infection, but it wasn't the influenza virus that screwed up my heart muscle, it was the white blood cells going apeshit trying to kill it.

If someone pushes you, and you start swinging your arms wildly to balance yourself, but end up falling in a different direction - why did you fall?

How hard did they push you? If they shoved you with only a micronewton if force and you fell, it's probably the fault of your overreaction.

If you took falling lessons as a kid, and you knew how to properly respond- following the push to a controlled fall, roll, or other redirection- you'd be fine. Sometimes the overreaction is the problem.

What are falling lessons? Judo?

Judo is good for learning to fall, otherwise not that much IMO.

I disagree. I was by far the smallest kid in my grade, but I took a couple of years of judo when I was 7. It was really useful as I grew up. A big equalizer for me. It does give you an intuitive sense of how to move and a shift your weight in your favor. Even if you fall, you end up falling on top of the other kid. As an adult and for personal defense I think Judo comes right after BJJ and wrestling.

Judo definitely helps. Any full contact martial art will, and Judo is the one with the most contact (at kids level) and lowest chance of serious injury. Wrestling too, but Judo typically covers more.

Lots of close contact will mean you're far less likely to panic in a fight situation. Most people have never been in a fight let alone hit.

Plus the fitness of course. Judo helps enormously with core strength.

BJJ borrows a lot from Judo, particularly the grappling.

I learned them as "ukemi"- I'm sure judo has them, though I was introduced via karate and later aikido.

Learning to snowboard on dry slopes gave me an instinct to fall with my elbows down and firsts up in front of me, so that I block my body with my arms, but have my fists clenched to protect my fingers. Obviously this does nothing if I don't fall forwards, but anyway.

I not sure whether this is the point you were making or not, but without the inflammation perhaps you would have simply died from the flu infection due to insufficient white blood cells around to kill it before it spread elsewhere in your body.

But it's perfectly possible to acknowledge the damage inflammation does while also acknowledging its necessity (or at least the possibility of its necessity). Just like e.g. you can acknowledge that chemotherapy drugs do damage to the body while still acknowledging that they're necessary sometimes.

Yeah - but that is kind of special case when talking about the problem with infections. It does not justify "All sickness".

Out of interest, how did you find out it was the white blood cells that were hurting the heart muscle? I have a history of myocarditis without any proper diagnosis.

Going into week 2 of the flu (immediately after getting vaccinated...). You've just freaked me out. Time for more research.

Infection actually also leads to inflammation, it's just a different kind. There is acute inflammation and chronic inflammation. Acute inflammation is good as it leads to your body healing. However, if the inflammation doesn't subside, that's when inflammation becomes chronic and eventually, disease occurs.

Why does pain seem to underlie all sickness?

Inflammation is likewise usually a symptom, not the cause. And in the case of muscular injuries, it is generally helpful to the healing process.

The kind of imbalance mentioned in the article isn't really a culprit in most instances of sickness.

Inflammation is the body's way to protect the affected part. Giving it some "extra cover".

Inflammation underlies sickness the way police underlie crime. I mean, you always see police around when there’s been a crime, right?

Isn't it part of the body's response to sickness? Why does screaming tend to underlie all stabbings?

Screaming doesn’t worsen stabbing wounds, directly. But inflammation does often (in all the examples I’ve read) worsen the triggering illness.

Chronic inflammation worsens chronic illness.

Acute inflammation is generally good. Ice should only be applied when the swelling is cutting off blood flow

Acute inflammation severely increases damage after moderately severe ischemic stroke [in rats], which can be prevented by blocking the acute inflammatory response. https://www.researchgate.net/publication/5257154_Interferon-...

Generally being the operative word. There are certainly cases where it's harmful.

And I thought it was interesting to provide such a counter example :-) HN generally appreciates factual knowledge

Ice baths seem to speed up recovery after exercise. But, the mechanisms by which this works are likely not limited to stopping inflammation.

There's actually little research that they do, beyond placebo. It works a lot better in animal trials than with humans. Probably because of differenced in our ability to actively cool ourselves.

https://bjsm.bmj.com/content/46/4/296

Could that be because when inflammation cures disease you don't get to read about it because nobody even looks to a healthy person?

Sure it does, panic & exertion makes you bleed out faster...

There’s a thing called the “Cell Danger Response”, where individual cells react to detecting danger to themselves in a somewhat selfish way, by inflaming and emitting purines (the chemicals cells also release when they lyse apart during apoptosis.) By the fact that other cells detect danger using these purines, this response is usually cascading in a local area. It lasts a long time; sometimes cells just never go out of this “red alert” mode once in it, because they’ve isolated themselves well-enough that they can never perceive the environment again to see that it’s all-clear.

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!)

———

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.)

I had never heard of this "cell danger response" before, and there's something about your description that does't smell right to this former cell biologist.

It's worth noting that so far, this seems to be a theory being advanced by one scientist:

https://www.ncbi.nlm.nih.gov/pubmed/?term=%22cell+danger+res...

This is not to say it's not true. But let's be careful here.

Careful? His comment is arguably the best I’ve read on HN this week.

The jargon term is https://en.wikipedia.org/wiki/Purinergic_signalling.

Personally, I find “Cell Danger Response” useful as a term to specifically reference one type of purinergic signalling. One which, yes, the author you link to is investigating, and invented the “Cell Danger Response” term for; but one which was already known as a type of purinergic signal (and an interesting, unique response to said signal) before their work. Their contribution is mostly in the disease linkages, not in providing evidence that the purine signal+response they call “Cell Danger Response” happens.

So, in other words, even if they’re P-hacking, the worst setback science might see is that these syndromes don’t turn out to be ameliorated by CDR-inhibiting enzymes after all.

However, I would note at least one distributed experiment by another “author”: the nootropics community has adopted https://en.wikipedia.org/wiki/Sulforaphane as a seemingly-effective treatment for the symptoms of autistic spectrum disorders (to the point that, with only their interest, it has become a common supplement with many available brands.) While we don’t understand sulforaphane very well, various journal papers suggest it has a role in modulating purine metabolism; and so the amateur biologists of the Internet have hypothesized that it is likely “cleaning” purinergic signalling molecules out of affected tissue for long enough for the cells to “relax” and stop screaming at one-another.

Do I understand correctly that sulforaphane could reduce the amount of purines released into the bloodstream? Is it a potential treatment for gout and other hyperuricemia conditions?

So, is the Cell Danger Response evoked by a certain root condition that cells are suffering from? Like unsufficient ATP production? Have you heard of any theories about that?

Every disease has some agent that causes inflammation. As already mentioned, not all inflammation is bad. Acute inflammation helps the body eliminate the agent and thus heal. When you're talking about inflammation that underlies all sickness, you're talking about chronic inflammation. This occurs when inflammation doesn't subside which leads to your body attacking itself. This is such an interesting topic. I've actually just written an article about leading diseases that are caused by inflammation, if you're interested: https://www.iamliesa.com/inflammatory-diseases-inflammation

Dave feldmans theory was very intriguing. Haven't read the article cuz of sign in.

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.

Inflammation can be a result of heart disease https://en.wikipedia.org/wiki/List_of_causes_of_death_by_rat...

Could it have to do with early humans being scavengers? I heard there is some scientific support for this hypothesis, and I can imagine this may have had a profound (and evolutionarily recent) effect on our immune system.

Could someone with more expertise shed a light?

Because we haven't learned to treat systemic diseases yet, where more than one factor needs to be shut down or modified to stop the progress.

https://outline.com/BXdFKX

Correlation is not causation.

My best understanding is that inflammation is a two street: It both promotes health problems and is, itself, caused by health issues.

Until we have a clearer handle on this dynamic, we are kind of stuck in our current "Jim, don't leave him in the hands of twentieth century medicine!" morass.

Is a paywall work around available?

Incognito mode.

https://en.wikipedia.org/wiki/Betteridge%27s_law_of_headline... I guess the grammar would need to be fixed, but otherwise it still works great!

Fighting inflammation has worked out much better for me than targeting any specific type of issue. As an example, bromelain, curbs sinus inflammation which reduces the number of sinus infections in some people.

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