
Why Does Inflammation Seem to Underlie All Sickness? - imartin2k
https://elemental.medium.com/why-does-inflammation-seem-to-underlie-all-sickness-64a2bef84f99
======
jniedrauer
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/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023714/)

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bamboozled
Thanks I’ve actually wondered about this for sometime!

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

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

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rjzzleep
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/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029099/)

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

[3]
[https://www.sciencedirect.com/science/article/pii/S002364380...](https://www.sciencedirect.com/science/article/pii/S0023643803002147)

~~~
gzer0
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...](https://www.cancer.org/cancer/chronic-myeloid-
leukemia/treating/targeted-therapies.html)

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rubicon33
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.

~~~
woodandsteel
>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.

~~~
rubicon33
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](https://en.wikipedia.org/wiki/Humorism)

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ferros
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.

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dghughes
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.

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_bxg1
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.

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

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

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zby
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.

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twic
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.

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im3w1l
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?

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mhluongo
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.

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nitrogen
What are falling lessons? Judo?

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

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huherto
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.

~~~
emmelaich
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.

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ummonk
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.

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

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

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

~~~
huffmsa
Chronic inflammation worsens chronic illness.

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

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catoc
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-...](https://www.researchgate.net/publication/5257154_Interferon-
Beta_Prevents_Cytokine-Induced_Neutrophil_Infiltration_and_Attenuates_Blood-
Brain_Barrier_Disruption)

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

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

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derefr
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.)

~~~
twic
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...](https://www.ncbi.nlm.nih.gov/pubmed/?term=%22cell+danger+response%22)

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

~~~
derefr
The jargon term is
[https://en.wikipedia.org/wiki/Purinergic_signalling](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](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.

~~~
darkerside
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?

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Iamliesa
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](https://www.iamliesa.com/inflammatory-diseases-inflammation)

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aszantu
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.

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known
Inflammation can be a result of heart disease
[https://en.wikipedia.org/wiki/List_of_causes_of_death_by_rat...](https://en.wikipedia.org/wiki/List_of_causes_of_death_by_rate)

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namenotrequired
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?

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kzrdude
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.

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sbmthakur
[https://outline.com/BXdFKX](https://outline.com/BXdFKX)

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DoreenMichele
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.

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quickthrower2
Is a paywall work around available?

~~~
rednerrus
Incognito mode.

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

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rasengan
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.

