Scientists: Protein IL-17 fights infection, acts on the brain, inducing anxiety | Hacker News Reader

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

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112 pointswglb46 comments

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.

Another aspect of this is that high levels of IL 17 can cause mania in bipolar patients.

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.

> 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.

I don’t know what you’re basing this on. Good psychiatrists absolutely “call themselves doctors” and definitely seek to exclude or treat organic causes of psychiatric symptoms. All the psychiatrists I know absolutely understand there’s a link between the immune system and mood disorders and will involve immunology/rheumatology for these things.

Your ideas about how psychiatry is practiced might have been correct in the 1950’s but they’re a world away from how it’s done in the 2020s.

> Good psychiatrists absolutely “call themselves doctors” and definitely seek to exclude or treat organic causes of psychiatric symptoms.

Well, yeah, you're just stating the contrapositive corollary to my assertion: that psychiatrists who don't "call themselves doctors" [i.e. who don't think of themselves as treating the patient's problem holistically first-and-foremost, and instead just do "talk therapy but you can prescribe"] are bad psychiatrists.

> Your ideas about how psychiatry is practiced might have been correct in the 1950’s

It might just be where I live (Canada), or the particular moment one will find a psychiatrist in their career to have openings to accept new patients to their private practice without a years-long waitlist... but the vast majority of psychiatrists I've interacted with personally as a patient, or have heard about interactions with through friends, have all had a distinctly 1950s mindset.

It might be because most of them have been seemingly nearly old enough to have gone to medical school in the 1950s. Most of them are only a year or two away from retirement.

(Which is frustrating, because it means I and others I know have to keep getting a referral to a new psychiatrist; wait-listing in to see them for an initial consult; seeing them for 1-2 years; and then getting dropped when the psychiatrist retires. And no, none of the psychiatrists I've been to have ever tried to create treatment continuity by cross-referring to another still-working psychiatrist; you just arrive at their office one day for an appointment you scheduled six months back to find it empty.)

But it also seems to imply that — despite the regular continuing education requirements for maintaining licensing — these folks don't seem to actually put the more-modern perspectives they've been exposed to into practice.

Interesting, I take risankizumab, which looks like it indirectly suppresses IL-17 (through suppressing IL-23A). I've been on it for a bit less than a year, and I can't say if I've had improved mood. Maybe? It definitely fixed the psoriasis. Might also have contributed to me getting sick more often, though.

I wish I had kept logs with some sort of self-screen depression instrument now (maybe the BDI? I don't like the PHQ-9). Might as well start now.

Recent risankizumab convert here :) Definitely happier now than I was before starting, but I'm sure some of that comes from the Crohn's not ruling my entire life anymore, lol. [knocks furiously on wood]

But I didn't know about the indirect IL-17 suppression. That's interesting!

Ketamine curbs IL-17 secretion pretty hard. Psoriasis tends to vanish pretty quick after a therapy session.

Ketamine really does reduce IL-17 secretion, and significantly.

Here come the sources. Links only for now. Hope to add a comment adding titles, authors etc.

https://www.oncotarget.com/article/18324/text/

https://www.frontiersin.org/journals/pharmacology/articles/1...

https://www.nature.com/articles/s41398-020-00933-z

Related / overview:

https://pmc.ncbi.nlm.nih.gov/articles/PMC10690603/

Whoa, just found this paper when digging up the links above – this is pretty wild!! https://academic.oup.com/ijnp/article/27/10/pyae041/7761949?...

Based on your knowledge and experiences, do you think the benefits are worth the potential side-effects?

I fully understand that after a certain point of disease severity, the right choices tend to become more apparent. However, I have been offered such medications in the past, but I have always refused.

From what I understand, many of the serious side-effects are rare. However, once Pandora is out of the box, it's not always easy to get her back inside.

If you have the kind of autoimmune issue severe enough that people are offering you biologics, the answer to "is it worth the risk?" is almost always yes, imo.

Unchecked inflammation is guaranteed to wreck your health, whereas treatments for that inflammation only have a slim chance of major side effects. For cancer risks specifically, it's worth considering that (1) you have a fighting chance to beat cancer, whereas an autoimmune condition can cause permanent and unfixable damage, and (2) autoimmune diseases are themselves associated with cancer risk. So for something like colitis, which is associated with bowel cancer, your overall odds of getting cancer are exponentially lower with treatment than without. (And less serious side effects usually go away when you stop the medication :P)

It's also worth noting that newer biologics are more like a sniper than a shotgun, so the immunosuppression is pretty targeted; still worth being careful, but it's not like the vulnerability that comes with, say, chemotherapy.

In my opinion, yes. Echoing the sibling comment, having a large amount of distributed skin lesions, or any joint pain at all makes one reconsider their options. Surface-level treatments might be very uncomfortable to apply and wear and provide only temporary and unstable relief, as well as UV sessions. Unless you live by the seaside or would like to go there several times a year to keep the skin clean, it's infeasible as a long-term solution. On the other hand, the quality of life improves immensely with injections - the symptoms _just_ disappear, which no diet, or lifestyle change, or application, or alternative medicine, or other supportive care can achieve in the majority of patients.

It goes without saying that your situation may be different, but most people I know opt for them meds, choosing Bimzelx, or a similar treatment (Taltz (ixekizumab) or Skyrizi (risankizumab)). The only downside is the cost, but it may be very well possible to wring it out of your insurance, especially in Europe.

I guess that is what makes things somewhat difficult for me. If I could not see my condition, then I wouldn't even know I had it. I have no symptoms that prevent me from doing anything I need to do in life (knock on wood). I am actually more on the mild side of the spectrum of disease severity.

So, that is why I find it unusual that doctors have offered biologics in the past. I do remember one doctor made a comment to me. She said it was unusual that I do not want biologics because most, if not all, of her patients beg for them regardless of the disease severity. Maybe she is getting kickbacks or something? I have no idea.

Basically, that is the root of my question. Are the risks worth it for someone that has maybe 1-2% coverage of lesions across their entire body? Sure, it'd be nice to go from 1-2% to 0%, I guess, but I cannot get a good understanding on the risks.

Pedantic note: Pandora was the woman who opened the box. Pandora was not in the box. The problems of the world were, along with hope. Maybe you're mixing the story with the phrase "the cat's out of the box" ?

Crap, you are right. I had a lapse in memory for a moment. Thank you though.

This is good to know. It looks like a "natural medicine" for this might be rosemary/sage: https://pmc.ncbi.nlm.nih.gov/articles/PMC3123037/

Is that „becoming happier“ also observed with TNF blockers like Adalimumab?

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/)

COQ10: Decreased plasma levels of IL-17 (https://www.clinicalnutritionespen.com/article/S2405-4577(22...)

Folic Acid: Reduces IL-17 (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

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.

Related paper on receptors: 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

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

Related: "N-acetylcysteine as a new prominent approach for treating psychiatric disorders" 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.

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.

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.

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.

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

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/

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-seroton...

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.

in case anyone wondering:

https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...

That’s a great question

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.

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.

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

A protein is a molecule What a strange reply

“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.

I guess depression makes for excellent self quaratine?

Yes, one would expect kin / group selection to play a role.

It generates extreme behavior. In both directions.

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

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.

A cup of mustard powder? What does it feel like and how did you come across this?

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 ;)

Yeah cause your point of reference is feeling like shit when you are feverish.

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://www.colorado.edu/asmagazine-archive/node/2080

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.

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".

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