20 ms·

Scientists: Protein IL-17 fights infection, acts on the brain, inducing anxiety

112 points by wglb 2y ago

wglb 2y ago
Related paper on receptors: https://www.cell.com/cell/abstract/S0092-8674(25)00279-X https://www.cell.com/cell/abstract/S0092-8674(25)00279-X Paper suggesting mood alteration: https://www.cell.com/cell/abstract/S0092-8674(25)00278-8 https://www.cell.com/cell/abstract/S0092-8674(25)00278-8
idontwantthis 2y ago
Any idea if this protein has any relation with seratonin? Could the effect of SSRIs be related in any way?
- boredemployee 2y ago
  in case anyone wondering: https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
- noncoml 2y ago
  That’s a great question
- xattt 2y ago
  Isoniazid has an antidepressant effect as a weak MAOI, but any interaction with IL-17 would be indirect and related to a reduced microbial load in TB.
- internet_rand0 2y ago
  seratonin is a molecule this is a protein[1] this question strikes me as asking if a quark has a relation with an atom [1] https://en.wikipedia.org/wiki/Interleukin_17 https://en.wikipedia.org/wiki/Interleukin_17
  - nartho 2y ago
    A protein is a molecule What a strange reply
    - deleted 2y ago
      [deleted]
    - jiggawatts 2y ago
      “Chemistry literacy” is very poor in the general public because it has very few everyday applications, so everything learnt at school just drops out of people’s brains. That’s why your hear nonsense like “It has chemicals in it!!!” It’s also why you regularly see science fiction where characters can grow in seconds, totally breaking the law of conservation of matter.
- carabiner 2y ago
  Serotonin has little relevance to depression and was more of a cute story doctors told patients in the '90s, that they were told by pharma reps.
  - api 2y ago
    AFAIK the truth is a little more complex: SSRIs do work for many people, but we don't really understand why and it's not as simple as 'more serotonin good.' They also don't work for everyone, and we don't understand why they don't work for some people either.
- dayvigo 2y ago
  Serotonin can decrease IL-17 production, and IL-17 is highly elevated in depressed patients. Inflammation is elevated in depressed patients more generally, but baseline IL-17 levels specifically appear to be a good predictor for antidepressant response[1]. Anti-depressants are pretty much universally anti-neuroinflammatory. [1]: https://pubmed.ncbi.nlm.nih.gov/28698115/ https://pubmed.ncbi.nlm.nih.gov/28698115/
- FollowingTheDao 2y ago
  Yes, cytokine like IL 17 increase an enzyme called IDO which pulls tryptophan away from the serotonin production pathway. https://www.researchgate.net/figure/Effect-of-IDO-on-serotonin-metabolism-in-humans_fig7_339439877 https://www.researchgate.net/figure/Effect-of-IDO-on-seroton...
ashoeafoot 2y ago
I guess depression makes for excellent self quaratine?
- biomcgary 2y ago
  Yes, one would expect kin / group selection to play a role.
- timewizard 2y ago
  It generates extreme behavior. In both directions.
jagaerglad 2y ago
this is rather amazing, I've always thought that my observation that I feel better in my brain after a good fever has to be imagination
- yapyap 2y ago
  Yeah cause your point of reference is feeling like shit when you are feverish.
  - gusgus01 2y ago
    Actually, there are some studies that show a anti-depressive effect from exposure to heat/fever like conditions. These are just two from a rudimentary Google search to check if I was remembering correctly. https://pmc.ncbi.nlm.nih.gov/articles/PMC6519523/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6519523/ https://www.colorado.edu/asmagazine-archive/node/2080 https://www.colorado.edu/asmagazine-archive/node/2080
- gehwartzen 2y ago
  I take mustard baths occasionally (about a cups worth) when I feel a cold or virus coming on which seems to kind of fast track clearing out whatever is causing it. Feel amazing after. Better than baseline as I’ve found a similar effect when not sick.
  - vosper 2y ago
    A cup of mustard powder? What does it feel like and how did you come across this?
    - gehwartzen 2y ago
      lol yes. I believe it’s an Ayurvedic treatment. You can get premixed versions which contain mustard and baking soda plus some other herbal ingredients. However if you end up doing them with any frequency it’s much more economical to just buy bulk ground yellow mustard powder from Amazon or similar. You soak in a lukewarm warm bath with the powder for about 10 minutes during which you will start to sweat like you never have before (so drink lots of water before and after). You then wrap yourself up in a towel and continue sweating for another 10 minutes or so followed by a brisk shower. I recommend giving it a try next time you feel a cold or something coming on. I find it very effective and worst you’ll sweat for a while and be out a cup of mustard ;)
bitwize 2y ago
Possibly related to: https://en.m.wikipedia.org/wiki/Sickness_behavior https://en.m.wikipedia.org/wiki/Sickness_behavior
eveningsteps 2y ago
Surprisingly enough, this partially exposes the link between depression and some of the autoimmunal diseases. One example is how patients with psoriasis have significantly elevated levels of proteins from the IL-17 family (namely, IL-17A, IL-17C, and IL-17F) - up to 4 to 8 times above nominal values. At the same time, bimekizumab, one of the bleeding-edge psoriasis and psoriatic arthritis treatments, suppresses production of IL-17A and IL-17F (methotrexate does that, too, albeit to a much smaller degree). As a result, people receiving IL-17 suppressors become happier over the course of years, and not only due to months-long remission - I had a chance to see this in one of the experimental treatment programs.
- FollowingTheDao 2y ago
  Another aspect of this is that high levels of IL 17 can cause mania in bipolar patients. https://pubmed.ncbi.nlm.nih.gov/27295856/ https://pubmed.ncbi.nlm.nih.gov/27295856/ I do not know why doctors are so hesitant to link the immune system and mood disorders. I have schizoaffective disorder and I see this expressing myself every time. For example, when I caught Covid, I had one of the worst psychotic episodes in my life. None of my doctors really cared about this important correlation. And I will scream this from the rooftops for as long as I can; mood disorders are immune disorders.
  - derefr 2y ago
    > I do not know why doctors are so hesitant to link the immune system and mood disorders. People who call themselves doctors — e.g. neurologists — generally aren't hesitant to do this. But psychiatrists — and even moreso, therapists — generally are. And psychiatrists+therapists lead the conversation on mood disorders, since that's who everyone is talking to about their mood disorders. IMHO it's just the hammer-and-nail thing. To a cardiologist, every medical problem is seen through a potentially cardiovascular lens; to an oncologist, every problem is a question of what type of cancer could cause it. Psychiatrists are technically medical doctors, but they spend their entire careers (after a few short years of school) focusing on psych cases; where these patients' problems either are purely psychological (e.g. conditioned-response, traumatic-response, coping/defensive, attachment-related, etc.), or at best "we don't know" the degree to which they're psychological vs organic. (If we can recognize a problem as purely organic from the outset, that problem doesn't end up in the hands of a psychiatrist!) And either way, they usually see good results in clinical practice from treating the patient's mind, rather than addressing organic signs/symptoms directly. Even when they prescribe medication, they're measuring their success on a mental basis (using questionnaire-based instruments used to gauge mental changes) rather than observing changes in e.g. measurable behavioral signs. The problems they're faced with, and the successes they have via these models, reinforce in psychiatrists a mind-centered mental model / worldview for psychiatric disease. (A model which is "the right one" to use in many psychological diseases! But not for many others.) And therapists aren't even medical doctors. They never learn much-at-all in school about potential organic causes of psychological (or medical) problems. They focus purely on this lens of "the mind", ignoring the lens of "the brain as an organ" entirely. This means that in clinical practice, when confronted with a problem that has both mental and organic aspects, a therapist will tend to ignore the organic aspects; and when confronted with a problem where the organic aspects are too large to ignore, the therapist will simply refer to a psychiatrist (or neurologist, maybe) — with no follow-up, and thereby, no way to end up learning what the patient's problem actually was and thereby evolving the neurological side of their understanding.
chaps 2y ago
This is interesting! I've been having some pretty bad intermittent panic attacks over the past year or so and a thing I've noticed is that I have general inflammation across my body along with the panic attacks. For a long while I thought it was an infected tooth, but with that fixed and the panic attacks still ongoing, I'm not sure! But this is a nice confirmation that there's some correlation.
- fsckboy 2y ago
  outside of the panic attacks, do you have periods of pleasurable excitement, fun-loving life of the party, or superproductive creative inspiration? consider "bipolar ii", and low dosage lithium can work wonders on both ends of the emotional spectrum. ianad and not diagnosing, just mentioning that lithium is a mineral salt found naturally in the freshwater in parts of the world, and in those places people have more stable moods.
mleonhard 2y ago
Related paper on the immune system triggering anxiety: "Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior" https://doi.org/10.1016/j.cell.2019.10.001 https://doi.org/10.1016/j.cell.2019.10.001 Related: "N-acetylcysteine as a new prominent approach for treating psychiatric disorders" https://doi.org/10.1111/bph.15456 https://doi.org/10.1111/bph.15456 section "2.3 Regulation of inflammatory mediators". N-acetylcysteine (NAC) is considered safe and is sold as a diet supplement in USA and many other countries. If you suffer from anxious feelings, 1200mg/day NAC may reduce them a lot.
fsckboy 2y ago
we should always start with the presumption that an effect like this is adaptive, as perhaps as simple as "when you're sick you should not sally forth to fight a dragon you heard about." And while in the modern world we tend to think "well, we can treat this with chemistry", don't be shocked if that course uncovers undesirable side effects down the road, or even direct effects like "hey, you're not fighting infection as effectively".
jujube69 2y ago
I read a study a while ago, the study found common vitamin deficiency in depressed humans. I researched more about it and looks like some of the deficiency in the vitamins in the study are correlated with higher IL-17 levels. Carnitine: Seems to have some effect in decreasing IL-17? Vitamin D: Highly impacts IL-17 (https://pmc.ncbi.nlm.nih.gov/articles/PMC4609465/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4609465/) COQ10: Decreased plasma levels of IL-17 (https://www.clinicalnutritionespen.com/article/S2405-4577(22)01049-X/fulltext https://www.clinicalnutritionespen.com/article/S2405-4577(22...) Folic Acid: Reduces IL-17 (https://pmc.ncbi.nlm.nih.gov/articles/PMC8839991/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8839991/) Lutein: I didn't find any study that seems to study the effect on IL-17 Citrulline: No relevant studies This is the study I'm referring to: https://www.nature.com/articles/s41398-023-02696-9 https://www.nature.com/articles/s41398-023-02696-9 I think we're getting closer to find some blood level correlations, so we can fix them! I can say for a fact when I take CoQ10, I feel my energy levels going up so it really has some effect.
funnym0nk3y 2y ago
There are multiple theories that focus on different ethiologies of depression. Besides brain networks, early life adversities, sleep disturbances and the now obsolete monoamine hypothesis I read about the inflamation hypothesis. On a higher level that ties into all the other theories quite well and I don't oppose it. But there has been research into TNF-a, IL-6, IL-4, COX-2, and so on. We know there is inflammation, but we don't know where it starts and why. SSRIs are antiinflammatory in general, but why? Is this a downstream effect? Where is the original target we want to hit? All those possible targets need to be verified by actual treatments. Treating the increased diabetes type 2 risk in depressed people is still advantagous but won't help the depression much. It's like changing tires on a broken car. Pushing is easier, but won't run by itself.
deleted 2y ago
[deleted]
elia_42 2y ago
Interesting. I personally experienced such feelings during periods when my immune system was working to protect me. I find the part of the article where the dual function of our immune system emerges really interesting: on the one hand its job is to fight pathogens, on the other hand to communicate with our brain via cytokines to protect ourselves and the community we live in.

112 points by wglb 2y ago

wglb 2y ago

Related paper on receptors: https://www.cell.com/cell/abstract/S0092-8674(25)00279-X https://www.cell.com/cell/abstract/S0092-8674(25)00279-X Paper suggesting mood alteration: https://www.cell.com/cell/abstract/S0092-8674(25)00278-8 https://www.cell.com/cell/abstract/S0092-8674(25)00278-8

idontwantthis 2y ago

Any idea if this protein has any relation with seratonin? Could the effect of SSRIs be related in any way?

boredemployee 2y ago
in case anyone wondering: https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
noncoml 2y ago
That’s a great question
xattt 2y ago
Isoniazid has an antidepressant effect as a weak MAOI, but any interaction with IL-17 would be indirect and related to a reduced microbial load in TB.
internet_rand0 2y ago
seratonin is a molecule this is a protein[1] this question strikes me as asking if a quark has a relation with an atom [1] https://en.wikipedia.org/wiki/Interleukin_17 https://en.wikipedia.org/wiki/Interleukin_17
- nartho 2y ago
  A protein is a molecule What a strange reply
  - deleted 2y ago
    [deleted]
  - jiggawatts 2y ago
    “Chemistry literacy” is very poor in the general public because it has very few everyday applications, so everything learnt at school just drops out of people’s brains. That’s why your hear nonsense like “It has chemicals in it!!!” It’s also why you regularly see science fiction where characters can grow in seconds, totally breaking the law of conservation of matter.
carabiner 2y ago
Serotonin has little relevance to depression and was more of a cute story doctors told patients in the '90s, that they were told by pharma reps.
- api 2y ago
  AFAIK the truth is a little more complex: SSRIs do work for many people, but we don't really understand why and it's not as simple as 'more serotonin good.' They also don't work for everyone, and we don't understand why they don't work for some people either.
dayvigo 2y ago
Serotonin can decrease IL-17 production, and IL-17 is highly elevated in depressed patients. Inflammation is elevated in depressed patients more generally, but baseline IL-17 levels specifically appear to be a good predictor for antidepressant response[1]. Anti-depressants are pretty much universally anti-neuroinflammatory. [1]: https://pubmed.ncbi.nlm.nih.gov/28698115/ https://pubmed.ncbi.nlm.nih.gov/28698115/
FollowingTheDao 2y ago
Yes, cytokine like IL 17 increase an enzyme called IDO which pulls tryptophan away from the serotonin production pathway. https://www.researchgate.net/figure/Effect-of-IDO-on-serotonin-metabolism-in-humans_fig7_339439877 https://www.researchgate.net/figure/Effect-of-IDO-on-seroton...

ashoeafoot 2y ago

I guess depression makes for excellent self quaratine?

biomcgary 2y ago
Yes, one would expect kin / group selection to play a role.
timewizard 2y ago
It generates extreme behavior. In both directions.

jagaerglad 2y ago

this is rather amazing, I've always thought that my observation that I feel better in my brain after a good fever has to be imagination

yapyap 2y ago
Yeah cause your point of reference is feeling like shit when you are feverish.
- gusgus01 2y ago
  Actually, there are some studies that show a anti-depressive effect from exposure to heat/fever like conditions. These are just two from a rudimentary Google search to check if I was remembering correctly. https://pmc.ncbi.nlm.nih.gov/articles/PMC6519523/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6519523/ https://www.colorado.edu/asmagazine-archive/node/2080 https://www.colorado.edu/asmagazine-archive/node/2080
gehwartzen 2y ago
I take mustard baths occasionally (about a cups worth) when I feel a cold or virus coming on which seems to kind of fast track clearing out whatever is causing it. Feel amazing after. Better than baseline as I’ve found a similar effect when not sick.
- vosper 2y ago
  A cup of mustard powder? What does it feel like and how did you come across this?
  - gehwartzen 2y ago
    lol yes. I believe it’s an Ayurvedic treatment. You can get premixed versions which contain mustard and baking soda plus some other herbal ingredients. However if you end up doing them with any frequency it’s much more economical to just buy bulk ground yellow mustard powder from Amazon or similar. You soak in a lukewarm warm bath with the powder for about 10 minutes during which you will start to sweat like you never have before (so drink lots of water before and after). You then wrap yourself up in a towel and continue sweating for another 10 minutes or so followed by a brisk shower. I recommend giving it a try next time you feel a cold or something coming on. I find it very effective and worst you’ll sweat for a while and be out a cup of mustard ;)

bitwize 2y ago

Possibly related to: https://en.m.wikipedia.org/wiki/Sickness_behavior https://en.m.wikipedia.org/wiki/Sickness_behavior

eveningsteps 2y ago

Surprisingly enough, this partially exposes the link between depression and some of the autoimmunal diseases. One example is how patients with psoriasis have significantly elevated levels of proteins from the IL-17 family (namely, IL-17A, IL-17C, and IL-17F) - up to 4 to 8 times above nominal values. At the same time, bimekizumab, one of the bleeding-edge psoriasis and psoriatic arthritis treatments, suppresses production of IL-17A and IL-17F (methotrexate does that, too, albeit to a much smaller degree). As a result, people receiving IL-17 suppressors become happier over the course of years, and not only due to months-long remission - I had a chance to see this in one of the experimental treatment programs.

FollowingTheDao 2y ago
Another aspect of this is that high levels of IL 17 can cause mania in bipolar patients. https://pubmed.ncbi.nlm.nih.gov/27295856/ https://pubmed.ncbi.nlm.nih.gov/27295856/ I do not know why doctors are so hesitant to link the immune system and mood disorders. I have schizoaffective disorder and I see this expressing myself every time. For example, when I caught Covid, I had one of the worst psychotic episodes in my life. None of my doctors really cared about this important correlation. And I will scream this from the rooftops for as long as I can; mood disorders are immune disorders.
- derefr 2y ago
  > I do not know why doctors are so hesitant to link the immune system and mood disorders. People who call themselves doctors — e.g. neurologists — generally aren't hesitant to do this. But psychiatrists — and even moreso, therapists — generally are. And psychiatrists+therapists lead the conversation on mood disorders, since that's who everyone is talking to about their mood disorders. IMHO it's just the hammer-and-nail thing. To a cardiologist, every medical problem is seen through a potentially cardiovascular lens; to an oncologist, every problem is a question of what type of cancer could cause it. Psychiatrists are technically medical doctors, but they spend their entire careers (after a few short years of school) focusing on psych cases; where these patients' problems either are purely psychological (e.g. conditioned-response, traumatic-response, coping/defensive, attachment-related, etc.), or at best "we don't know" the degree to which they're psychological vs organic. (If we can recognize a problem as purely organic from the outset, that problem doesn't end up in the hands of a psychiatrist!) And either way, they usually see good results in clinical practice from treating the patient's mind, rather than addressing organic signs/symptoms directly. Even when they prescribe medication, they're measuring their success on a mental basis (using questionnaire-based instruments used to gauge mental changes) rather than observing changes in e.g. measurable behavioral signs. The problems they're faced with, and the successes they have via these models, reinforce in psychiatrists a mind-centered mental model / worldview for psychiatric disease. (A model which is "the right one" to use in many psychological diseases! But not for many others.) And therapists aren't even medical doctors. They never learn much-at-all in school about potential organic causes of psychological (or medical) problems. They focus purely on this lens of "the mind", ignoring the lens of "the brain as an organ" entirely. This means that in clinical practice, when confronted with a problem that has both mental and organic aspects, a therapist will tend to ignore the organic aspects; and when confronted with a problem where the organic aspects are too large to ignore, the therapist will simply refer to a psychiatrist (or neurologist, maybe) — with no follow-up, and thereby, no way to end up learning what the patient's problem actually was and thereby evolving the neurological side of their understanding.

chaps 2y ago

This is interesting! I've been having some pretty bad intermittent panic attacks over the past year or so and a thing I've noticed is that I have general inflammation across my body along with the panic attacks. For a long while I thought it was an infected tooth, but with that fixed and the panic attacks still ongoing, I'm not sure! But this is a nice confirmation that there's some correlation.

fsckboy 2y ago
outside of the panic attacks, do you have periods of pleasurable excitement, fun-loving life of the party, or superproductive creative inspiration? consider "bipolar ii", and low dosage lithium can work wonders on both ends of the emotional spectrum. ianad and not diagnosing, just mentioning that lithium is a mineral salt found naturally in the freshwater in parts of the world, and in those places people have more stable moods.

mleonhard 2y ago

Related paper on the immune system triggering anxiety: "Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior" https://doi.org/10.1016/j.cell.2019.10.001 https://doi.org/10.1016/j.cell.2019.10.001 Related: "N-acetylcysteine as a new prominent approach for treating psychiatric disorders" https://doi.org/10.1111/bph.15456 https://doi.org/10.1111/bph.15456 section "2.3 Regulation of inflammatory mediators". N-acetylcysteine (NAC) is considered safe and is sold as a diet supplement in USA and many other countries. If you suffer from anxious feelings, 1200mg/day NAC may reduce them a lot.

fsckboy 2y ago

we should always start with the presumption that an effect like this is adaptive, as perhaps as simple as "when you're sick you should not sally forth to fight a dragon you heard about." And while in the modern world we tend to think "well, we can treat this with chemistry", don't be shocked if that course uncovers undesirable side effects down the road, or even direct effects like "hey, you're not fighting infection as effectively".

jujube69 2y ago

I read a study a while ago, the study found common vitamin deficiency in depressed humans. I researched more about it and looks like some of the deficiency in the vitamins in the study are correlated with higher IL-17 levels. Carnitine: Seems to have some effect in decreasing IL-17? Vitamin D: Highly impacts IL-17 (https://pmc.ncbi.nlm.nih.gov/articles/PMC4609465/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4609465/) COQ10: Decreased plasma levels of IL-17 (https://www.clinicalnutritionespen.com/article/S2405-4577(22)01049-X/fulltext https://www.clinicalnutritionespen.com/article/S2405-4577(22...) Folic Acid: Reduces IL-17 (https://pmc.ncbi.nlm.nih.gov/articles/PMC8839991/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8839991/) Lutein: I didn't find any study that seems to study the effect on IL-17 Citrulline: No relevant studies This is the study I'm referring to: https://www.nature.com/articles/s41398-023-02696-9 https://www.nature.com/articles/s41398-023-02696-9 I think we're getting closer to find some blood level correlations, so we can fix them! I can say for a fact when I take CoQ10, I feel my energy levels going up so it really has some effect.

funnym0nk3y 2y ago

There are multiple theories that focus on different ethiologies of depression. Besides brain networks, early life adversities, sleep disturbances and the now obsolete monoamine hypothesis I read about the inflamation hypothesis. On a higher level that ties into all the other theories quite well and I don't oppose it. But there has been research into TNF-a, IL-6, IL-4, COX-2, and so on. We know there is inflammation, but we don't know where it starts and why. SSRIs are antiinflammatory in general, but why? Is this a downstream effect? Where is the original target we want to hit? All those possible targets need to be verified by actual treatments. Treating the increased diabetes type 2 risk in depressed people is still advantagous but won't help the depression much. It's like changing tires on a broken car. Pushing is easier, but won't run by itself.

deleted 2y ago

[deleted]

elia_42 2y ago

Interesting. I personally experienced such feelings during periods when my immune system was working to protect me. I find the part of the article where the dual function of our immune system emerges really interesting: on the one hand its job is to fight pathogens, on the other hand to communicate with our brain via cytokines to protect ourselves and the community we live in.