IL-8, The Inflammatory Mediator That Is 220% + Higher In PWP Cerebrospinal Fluid Than In Control Subjects And Possible Ways To Deal With It

[chartist]

In a recent reply post to forum member Parkie13 (Mary) I was discussing the chemokine Interleukin-8 (IL-8) and its relationship to PD and Multiple Sclerosis(MS) which I had only recently read about myself. The conversation got going because the post was discussing the possibility that MS may be caused by a virus and that in a similar line of thinking, is there a possibility that PD could potentially be caused by a virus or other pathogen? After doing some reading on this idea, I decided to do a post with a little more detail than the reply that I wrote to Mary and try and expand on the role of IL-8 in PD and find ideas on how to potentially inhibit or antagonize IL-8 in an effort to reduce its very negative effects in promoting neuroinflammation and consequently neurodegeneration in PD since it is seldom mentioned or discussed, if at all, in regards to PD even though it is clearly "a very major player" in the disease process! I have not seen one post on this forum discussing it, but it should definitely be a target for therapy in PD once you read about its role!

From what I have read so far, the chemokine IL-8 is part of the inflammatory process in both PD and MS, but It does not have direct inflammatory qualities itself, but rather recruits neutrophils which ultimately call upon other inflammatory mediators such as NF Kappa b, tnf alpha and inflammatory cytokines such as IL-1, IL-6 and IL-17 which are all known to be active in PD and MS based on many studies about the inflammatory cascade process with both diseases. The following abstract clearly illustrates that IL-8 is low in the serum of PWP.

ncbi.nlm.nih.gov/pubmed/270...

Interestingly, in serum testing of PD and MS patients it is shown that IL-8 levels are actually lower than comparable control groups. At first glance this looks like a good thing since less IL-8 likely means less neutrophils and consequently less inflammatory mediators and less of the damage that they are known to cause when they are chronically activated as they are in PD and MS. Upon closer inspection it turns out that while serum levels of IL-8 are lower, the levels in the brain /cerebrospinal fluid (CSF) compartment are definitely very elevated! As shown in the following study, by as much as 220% or more in PWP! This is more than a little significant and this compartment is where much of the damage is done in both MS and PD! Here is a link to a study that shows that IL-8 is definitely at very elevated levels in the CSF of PD and AD patients also! :

ncbi.nlm.nih.gov/pmc/articl...

The following study clearly suggests that IL-8 is a very major player in the disease process of PD and a definite potential target in the CSF! Here is a direct quote from this study below :

' PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD.'

ncbi.nlm.nih.gov/pmc/articl...

Here is a chart from the above study that illustrates some of the inflammatory mediators in serum and CSF of PWP :

Table 1

CSF TNF, CRP, IL-8, IL-6, α-synuclein, and Aβ levels were disrupted in PD versus HC

Quadratic effectHCPD

Serum analyteF statisticsp valueF statisticsp value

 TNFF (1,5) = 0.060.82F (1,11) = 0.020.89

 IFNγF (1,5) = 0.480.52F (1,11) = 1.160.31

 NGALF (1,5) = 2.240.19F (1,11) = 1.370.27

 CRPF (1,5) = 0.090.78F (1,11) = 3.620.08

 IL-6F (1,5) = 5.370.07F (1,11) = 0.100.76

 IL-8F (1,5) = 0.110.76F (1,11) = 2.880.12

CSF AnalyteF statisticsp valueF statisticsp value

 TNFF (1,5) = 5.390.07F (1,10) = 7.470.02

 IFNγF (1,5) = 0.000.99F (1,10) = 1.240.29

 NGALF (1,5) = 0.160.71F (1,10) = 0.900.37

 CRPF (1,5) = 1.670.25F (1,10) = 6.510.03

 IL-6F (1,5) = 15.000.01F (1,10) = 2.970.12

 IL-8F (1,5) = 1.280.31F (1,10) = 8.450.02

 α-synucleinF (1,5) = 3.890.11F (1,11) = 6.020.03

 Aβ40F (1,5) = 26.360.004F (1,11) = 8.190.02

 Aβ42F (1,5) = 5.600.06F (1,11) = 11.600.006

Also of interest as regards IL-8 is that "thiamine deficiency" can cause elevation of IL-8 according to the following study!

ncbi.nlm.nih.gov/pmc/articl...

Since IL-8 is so active in the CSF of MS and PD and is at such significantly elevated levels it is possible that researchers at some point may consider the chemokine IL-8 a potential target in the treatment of either disease and expand on the current limited studies. Since it is the IL-8 in the CSF that would likely be targeted, it would be necessary to find molecules that are capable of passing through the blood brain barrier (BBB) and this is a bit of a problem because the BBB is supposed to keep many molecules out. Even if you have a molecule that is capable of crossing the BBB, that molecule will also have to have the ability to antagonize or inhibit IL-8 once it crosses the BBB and again this adds a further degree of difficulty in locating such a molecule.Such a molecule would also have to have a very good safety profile since it will be active in the brain/CSF and this adds a further degree of difficulty in trying to locate such a molecule.

So any candidate molecule will need to have the ability to cross the BBB in amounts sufficient enough to be capable of interacting with the chemokine IL-8 effectively, this molecule will also be required to have a very good safety profile so it does not do damage to brain cells, it must be easily available to the masses and it has to be able to antagonize or inhibit the target, IL-8. Ideally, this molecule will not require two decades of testing to establish its safety for the intended purpose of targeting IL-8 in the brain/CSF. Lastly, this molecule will hopefully not be so expensive as to make it too cost prohibitive to be a practical treatment option for MS and PD patients.

With those criteria established, the search for such a molecule or molecules begins. On this forum we frequently discuss magnesium in many forms for different uses by PWP to help alleviate PD symptoms and medication symptoms. Many members report good effects from these multiple forms of magnesium including a topically applied form called magnesium chloride oil or mag oil (MO) which has shown benefit for rapid relief of muscle cramps and tight muscles and pains of various origins and causes. We also talk about three specific forms of magnesium that have shown the ability to cross the BBB better than other forms of magnesium so far.

Three forms of magnesium that have shown the ability to effectively cross the BBB are Magnesium Aspartate which has shown the ability to rapidly cross the BBB as well as the ability to be rapidly taken up by other areas of the body. The second form of magnesium that is purported to be able to cross the BBB is Magnesium L Threonate and it is sold almost as a specialty form that is able to cross the BBB, but human studies are not its strong suit. The third form of magnesium that has shown itself to be able to cross the BBB is Magnesium Taurate. This third form of magnesium contains taurine and as has been discussed previously on the forum. Taurine is also considered to be helpful in PD and has some neuroprotective qualities, but also important is that taurine can cross the BBB and inhibit IL-8. So these are molecules which all have a very good safety profile, can cross the BBB, have been around for quite awhile, are relatively inexpensive, are easily attainable, have multiple other health potential, are often low, insufficient or deficient in humans and they all antagonize or inhibit the chemokine IL-8! Another molecule with the proven ability to cross the BBB, has a very good safety profile, is relatively inexpensive, has already shown benefit in some PWP, is readily available in multiple forms and inhibits or antagonizes IL-8 is our very well known Thiamine HCL!

Another popular supplement that has shown potential to cross the BBB and inhibit IL-8 is Pine Bark Extract (PBE) of which there is a patented form that sells at a substantially higher price than other pine bark extracts. Many studies have touted the health benefits of PBE and it too has a very good safety profile. The unpatented forms of PBE are readily available and relatively inexpensive. For those of you who are familiar with PBE, you are also probably aware that Grape Seed Extract (GSE), is thought to have very similar effects to PBE and in this case, GSE has similarities in that it is able to cross the BBB and inhibit IL-8. GSE is not to be confused with Grapefruit Seed Extract, which is of course derived from grapefruit. Like PBE, GSE has also shown neuroprotective effects.

One supplement, though having an as yet undiscovered method of action that has shown the ability to lower the gene expression of IL-8 are probiotics as outlined in the following study :

ams.ac.ir/AIM/NEWPUB/18/21/...

A supplement that I often describe as "one of my favorite supplements" and discuss frequently on this forum, melatonin, is already established for its ability to cross the BBB and this is one way it is able to provide neuroprotection in humans and animals. Melatonin has a very good safety profile, is readily available in the US over the counter, is very inexpensive, is sometimes prescribed by doctors for various reasons, is naturally produced in the body, is a highly potent antioxidant on its own, but is also capable of reducing and recycling other antioxidants and even more importantly increases the bodies own highly potent antioxidants such as catalase, glutathione and super oxide dismutase. Very importantly, melatonin is a known IL-8 inhibitor! Here is an abstract that shows that melatonin inhibits IL-8 and other inflammatory mediators that are known to be active in PD :

ncbi.nlm.nih.gov/pubmed/219...

The following abstract shows that melatonin is able to gain entry and effect repair in the brain and actually can repair or protect the BBB against damage!

ncbi.nlm.nih.gov/pubmed/280...

The fact that we have many melatonin receptors in multiple locations throughout the body illustrates that the human body has uses for melatonin of which we are still learning about. Melatonin has shown many health benefits in humans one of which is its anticarcinogenic effects in certain cancers that it has been tested for in humans. Melatonin also has protective effects in the major organs including the brain, heart, lungs, liver kidneys, skin and eyes! Melatonin can also help repair brain injury from stroke. Well, I did say it was one of my favorite supplements didn't I !

Lastly, another supplement that we have discussed often on the forum and I have previously written an extensive post about its effects in PWP, vitamin D. Yes, beyond all of the positives I wrote about it as it relates to PD, it also meets the criteria for this post! Vitamin D metabolites cross the BBB and can also help protect the BBB against damage, has a very good safety profile, is generally deficient or insufficient in PWP, is inexpensive, is readily available, is some times prescribed by doctors, is easy to take, has shown itself to have multiple potential health benefits and of course happens to be an IL-8 inhibitor as well as an inhibitor of other inflammatory mediators typically seen at elevated levels in PD as outlined in the following study.

ncbi.nlm.nih.gov/pmc/articl...

I think that going after IL-8 which is higher up in the PD and MS inflammatory cascade can be effective because by doing that, it can prevent or significantly lessen the chances for the inflammatory mediators lower in the cascade from ever becoming activated in the first place, as they can be very damaging! While it would be crazy to try and block IL-8, I believe that the majority of these anti- IL-8 supplements are relatively weak inhibitors of IL-8, but I believe the right combination of these supplements, may be just strong enough to try and return the chemokine IL-8 closer to its native levels as seen in control groups which may be just enough inhibition to very significantly limit neutrophil activation and consequently a very meaningful reduction of the inflammatory mediators below IL-8 in the inflammatory cascade that is seen in PD and MS.

As a side note related to previous discussions on the forum regarding reports of the common antibiotic Doxycycline being possibly helpful at reducing PD symptoms, doxy happens to be an IL-8 inhibitor, it crosses the blood brain barrier and can perform its antibiotic actions there also!

Given all of the above, it appears that this forum, has been on a very good track in terms of finding things that may be helpful for PWP and possibly to a degree, higher than any of us may have previously thought or knew! Just look at these nine supplements and how often they have been discussed on the forum and now we know that they all have two other very important activities of crossing the BBB and inhibiting IL-8!

I'm sure there are other molecules like these that may qualify for the proposed purpose, but these nine seem like an excellent starting point and now that we know that the chemokine IL-8 may be a potential target in PD and MS or at least it should be, we can continue the search for other potential molecules which may show promise in their abilities to inhibit the very inflammatory IL-8 chemokine in the brain/CSF!

Regarding the idea that MS or PD may in some cases, have an as yet undiscovered viral or other pathogenic component as a driving force, none has yet been discovered and until such a pathogen might be discovered, you can not just start randomly throwing antiviral or antibacterial meds at PD or MS without knowing which antiviral or antibiotic might be the correct one to use. If such an avenue were to be pursued in a laboratory setting, one possible option would be to consider using colloidal silver nanoparticles (AgNPs) which are already known to cross the BBB, have a very good safety profile, are readily available over the counter, are relatively inexpensive, have the ability to neutralize a huge number of pathogens of both bacterial and viral origin and is relatively gentle to normal human cells while showing very good potency against hundreds of pathogens including some fungus and parasitic pathogens. One difference or advantage with AgNPs is that it can be given without knowing what the potential pathogen is. It either neutralizes it or it doesn't, but it is not likely to do any significant damage to normal cells at the dosing levels required to neutralize most viral and bacterial pathogens it has been tested against. As far as current testing of AgNPs and the brain, there are only PD mouse model studies so far and those show that AgNPs have antiinflammatory effects in the brain because AgNPs aid in the synthesis of the potent antiinflammatory gas signaling molecule, Hydrogen Sulfide (H2S). H2S was previously thought to be toxic at relatively low levels, but has since been found to be potently antiinflammatory at the right levels as produced in the body and because this H2S is being produced in the brain, it demonstrates its effects right there and it is well established that inflammation in the brain is a major driving force in both PD and MS. Here is a link to a mouse PD model study using silver nanoparticles to good effect :

ncbi.nlm.nih.gov/pmc/articl...

I am not suggesting that anyone try any of the above, I would just like you to open your mind further to the possibilities of looking at previously undiscussed options in fighting certain inflammatory aspects of PD! These inflammatory aspects of PD also give rise to reactive oxygen species, oxidative stress and other radicals which all feed off of each other in a vicious cycle that needs to be reduced, controlled or broken in order to interrupt the disease process.

Art

I will list additional supplements that show the potential to inhibit IL-8 and are able to cross the BBB here for future reference. The first addition is Niacin by forum member Gio!

Member's list of IL-8 inhibitors that are purported to cross the BBB :

1. Niacin - Member Gio contributed this one along with study in his post above.

2. Icariin a derivative of the herb Horny Goat Weed. Forum member LAJ12345 including mentioning symptom benefit very early on after starting her husband on it.

3. Sildenafil - This common prescription med was suggested by member bone60

4. Curcumin derived from the herb Turmeric and should come as no surprise! Art

5. Carnosine - Again, this one from LAJ12345 with possible synergy with Icariin.

6. L-Theanine - Used for relaxation, stress relief and anxiety among other benefits. Art

7. EGCG - From tea crosses the BBB and inhibits IL-8, IL-6 & TNF alpha. Art

8. Baicalin - Derived from Scutellaria Baicalensis and meets the criteria. silverstrov

9. Boswellia Serrata (BS) - In all of its forms is an inhibitor of IL-8 and crosses the BBB. Other forms include AKBA which is considered more potent than standard extract. A more potent form of Boswellia is called Apres Flex but is harder to find. BS is a potent antiinflammatory and is often used in glucosamine multi supplements for its pain relieving effects. Some refer to BS as frankincense, but that is actually a more specific form of BS. Art

10. Hesperidin / Hesperitin- from citrus fruit inner peel. Antioxidant, Antiinflammatory and antidiabetic. Anti-psoriasis. Art

11. Fisetin - This one meets the criteria to be on this list and was contributed by forum member JerMan22!

12. Selenium crosses the blood brain barrier and inhibits IL-8. Art

[parkie13]

It's going to take me awhile to read it. Thank you Art

[bassofspades]

Thanks for taking the time to research and compile this information!

[Oceanflow]

Thank you for taking the time to write such a thorough and potentially helpful report! Since my sister has MS I will share this post with her as well.

[chartist in reply to Oceanflow]

Oceanflow,

You're welcome!

A close friend of mine has MS also and I was reading up on it and that is how I also found out about the role of IL-8 in PD! IL-8 is active in many disease states, but neurological disorders are where it seems to be elevated in the CSF as opposed to a disease like psoriasis where IL-8 is elevated in the serum and skin. One of the main points of that post is that IL-8 is higher up in the inflammatory cascade, so if you can inhibit it, that could be possibly more effective than trying to inhibit multiple down stream inflammatory mediators as targets.

Art

[Gioc]

Thank you Art,

In my opinion, let's not forget the good and old B3 niacin that has all the required requirements and as an anti-inflammatory is very studied. If used with a good dietary and supplement will solve “ deficiencies “ with some benefit.

In fact niacin is studied in relation to PD a lot, (just search the web). Like everything else is very experimental.

scienceofparkinsons.com/tag...

[chartist in reply to Gioc]

You're welcome Gio!

It gets a little confusing for me, but I believe you are correct! Niacin gets converted to nicotinamide/niacinamide in the liver :

pdfs.semanticscholar.org/ae...

Nicotinamide/niacinamide are inhibitors of IL-8 :

ncbi.nlm.nih.gov/pubmed/197...

Nicotinamide freely crosses the BBB :

ncbi.nlm.nih.gov/pmc/articl...

So based on the above, we now have our tenth supplement that fills the bill and again it is one we have previously discussed on the forum showing once again that this forum is consistently finding things that are helpful for PD in more ways than we may have thought !

Thank you, Gio! I have added your niacin choice to the original post above^^^^^.

Art

[Gioc in reply to chartist]

For lovers of the genre a recent very technical study on the anti-inflammatory properties of niacin or vitamin B3 NA which is perhaps the most studied for PD.

“Niacin Ameliorates Neuro-Inflammation in Parkinson’s Disease via GPR109A”

ncbi.nlm.nih.gov/pmc/articl...

[Gioc in reply to Gioc]

For information, besides being anti-inflammatory, Niacin would seem to have anticancer properties for some types of cancer.

ncbi.nlm.nih.gov/m/pubmed/2...

[Fed1000 in reply to Gioc]

Hi Gio, do you have results with B3 riboside di nicotinamide? What type are you using? Thanks

[Gioc in reply to Fed1000]

No, I use, only occasionally, the good, old, healthy and inexpensive b3 nicotinic acid called niacin which gives the so-called "flush". In other words, sometimes with a redness and itching that lasts a little over half an hour which means that it works as an anti-inflammatory.

ncbi.nlm.nih.gov/pmc/articl...

I take 500mg a day maximum, for a month, but the dose used in various research is 250mg a day.

[gwendolinej]

Thank you Art, you are a class act. You give so much support to us. It's because you care, as so many on this forum do.

[chartist in reply to gwendolinej]

gwendolinej,

Thank you very much for saying so! I think it is interesting that almost all of the supplements on that list have been mentioned frequently on this forum for various reasons related to PD and now we have another reason to consider them beneficial!

Art

[Astra7]

Thanks for the interesting info. Wish we could get it all in just one pill!

[MarionP]

You know after weaving through it all, the common element of practicality seems to funnel down to thiamine plus magnesium plus calcium (necessary component to allow the magnesium to work).

Meanwhile: has anyone but me noticed that a natural (one of the very few) sources of MAOI comes from eating a brazil nut? Wish I'd have waited to buy some before telling anyone. My point is it is likely to be a gentle low effective dose (thus low risk) central point of assistance in the 5htp and dopaminergic complex, including across the BBB, the advantage of subtle help being that it is highly titrat-able so as to allow individuals to comfortably experiment with with very low risk.

[mauigirl18]

So thankful for your time and research and that we get to benefit from this.

[chartist in reply to mauigirl18]

Thank you, mauigirl18!

Art

[LAJ12345]

This is great, thanks!

Where do you get your silver nano particles and what brand is it please?

[chartist in reply to LAJ12345]

I purchased a computer controlled generator and heated magnetic stirrer plate with a silver bar electrode and make my own because it is very expensive to by silver products at retail prices when you are actually trying to treat a health issue and with retail products, you really have no idea if they are what they say they are. Most retail products are ionic silver with only a few exceptions although they claim to be colloidal silver. Generally if the product comes in a blue, brown or amber bottle they are ionic silver and ionic silver seems to be more toxic to normal human cells. Another indication that the product is ionic silver is if the product is the clear color of water. Silver nanoparticles can vary in color depending on how much silver is in it from baby shampoo yellow to dark coffee brown. Yellow AGNPs are usually around 20 ppm whereas the dark brown AGNPs can be anywhere from about 150 ppm up to over a thousand ppm. I generally make 320 ppm which looks like black coffee or I make 30 ppm which looks yellow/amber in color and slightly darker than the baby shampoo yellow 20 ppm.

As an example, it costs me less than a dollar to make a half liter of 20 or 30 ppm silver nanoparticles whereas a typical online seller is selling a 500 ml bottle of 20 ppm for around

$57!

amazon.com/MesoSilver-Collo...

What concerns me about this product is the fact that they claim their particle size is less than 1 nm and they say that like it is a good thing, but if it really is that small of a particle size it will be more harmful to normal human cells according to recent studies. In any case, these products seem ridiculously expensive for what they are.

Art

[LAJ12345 in reply to chartist]

Thanks! How much was the equipment to make it?

[chartist in reply to LAJ12345]

The generator was around $350, the silver bar was about $35 and will last for years under one household usage, the hot plate magnetic stirrer was around $140 , a basic beaker set was around $25 and an extra large lid/electrode holder to fit a one liter beaker about $35. So roughly over $600 with tax and shipping. I got a few extra things like a digital thermometer, a digital scale and an assortment of different size mason jars for storage and a few other small items which probably put me over $700. At the cost of retail silver products, my initial outlay was covered years ago. The guy who makes these is semi-retired and usually only makes them as they are ordered now, assuming he is still making them at all. I bought two because I knew he would not be making these forever and as far as I have seen, to buy something similar from any where that might have something like it would cost about a $1000 for just the unit. Any other unit under $500 usually only has a capacitor, a diode, an on off switch, a step down transformer and a small on off light and are pretty much junk with no ability to make different ppm concentrations or multiple batch sizes. If you could see what is inside of this unit compared to anything under $500 is simply unbelievable! It is a complete preprogrammed processor and makes very consistent batches.

Art

[LAJ12345 in reply to chartist]

That sounds a bit complicated and expensive for me unfortunately🥺

[chartist in reply to LAJ12345]

Actually it is fairly simple to do once you've made a few batches, but yes, a bit on the pricey side unless you have a specific purpose('s) in mind or plan to make it for others.

Art

[Despe]

Art,

Thank you for your research! You never seize to amaze me with your knowledge and desire to help. You are a valuable member of this forum, and I have learned so much from you. As I have written before, my husband hasn't had any cramps ever since you introduced me/us to Magnesium Oil. He also takes most of the supplements/minerals you mentioned, and they have helped him tremendously.

On another tune, his B1 vials are finished, and we won't refill the prescription. We decided to give Allithiamine a try, at least finish one bottle and go back to oral B1 HCL later.

[chartist in reply to Despe]

Thank you, Despe!

I remember a few forum members who mentioned using MO to good effect? I look forward to your updates on how it is working out for your husband as we don't have any data on that one yet.

Art

[LAJ12345]

It seems our new favourite icariin from horny goat weed also inhibits the gene expression of IL-8 in HaCaT cells. I’m not sure if HaTCa cells are relevant? It seems to be having a great effect on my husband who has had a huge reduction in apathy and increase in motivation. I think due to HGW.

ncbi.nlm.nih.gov/pmc/articl...

“The ICA administration also inhibited the gene expression of IL-1β, IL-8, TACR1 and ICAM-1 in HaCaT cells in a doseand time-dependent manner.”

[chartist in reply to LAJ12345]

I like that it affects gene expression of IL-8. It would also need to cross the BBB and if it can do that, it should be on the list above! Thank you for that one!

[LAJ12345 in reply to chartist]

I think it can

ncbi.nlm.nih.gov/pubmed/257...

“

Icariin (ICA), a flavonoid extracted from the traditional Chinese herb Herba Epimedii that can freely cross the blood-brain barrier, inhibits neuroinflammation and attenuates oxidative stress damage. “

It certainly is one of only 2 things that has had a quick and noticeable effect on my husband in only 3 days. The other being Hardy’s daily essential nutrients.

[chartist in reply to LAJ12345]

Well they don't come right out and say that it crosses the BBB, but it seems in order to do what they are describing, it must have that ability and as you say, the fast response seems like another form of confirmation, so I added your find to the original post above to keep that information in one place making it easier for any one who reads that post at any time! Thank you for that LAJ12345! I will ad Gio's niacin to the list also!

Art

[Despe in reply to LAJ12345]

I observed minor improvements on motivation and MAJOR improvements on libido. We are on the right path LAJ! Thinking about starting it myself. . .hahaha.

[LAJ12345 in reply to Despe]

Hee hee! He isn’t aware of what he is taking as he is not a bit interested and happy for me to do the research and try him on things so definitely not placebo!😁

This week we went away on holiday and it was the first time in about 5 years that he hasn’t got sick after 3 days of holiday and taken to his sick bed. Instead he was off fishing, researching spots to go etc. amazing!

[Despe in reply to LAJ12345]

I envy you. I am trying to prepare him psychologically for a transatlantic trip next year. See if HGW works that well.

[Zella23]

Wow what an amazing carefully researched and informative post that will take me a while to carefully read through! Interesting that lots of supplements we ve known about are included in the above. Thank you so much that.

Between babysitting, reading my book club book ( needed by tomorrow) and last minute complicated knitting requested by my grandson I ll try and digest the info when I have time.

Many thanks!

[ConnieD]

Thank you for this wealth of information Art!!

[Kia17]

Art

Thank you for the valuable information. Kia

[Kia17]

The following Inhibit IL-8

IL-8 production is caused by the transcription factor NF-κB, and is induced by IL-1 and TNF, So anything that will inhibit these will also likely lessen IL-8..

Calorie Restriction

Fasting

Wim Hof Breathing/Meditation

Quercetin

Bromelain (promising, removes receptors – CD128a+b from neutrophils – unique mechanism?)

Probiotics: B. infantis, L. casei and L. lactis ,B. Longum, L. Bulgaricus ,S. Boulardii ,B. subtilis

Resveratrol (500mg, with 5g leucine)

Luteolin

Apigenin

Aspirin

Cinnamon :Sodium Benzoate

Fisetin ,not activated basophils

Cod liver/fish oil

Licorice

Curcumin

Black Cumin Seed Oil/Thymoquinone

Andrographolide (by inhibiting NF-kB)

Vitamin D3

Jasmine Tea/EGCG

Zinc

Red Yeast Rice/Statins

Theaflavins (“Potent”)

Artemisinin

Vitamin E (alpha-tocopherol prevents UVA-induced IL-8 increase

selfhack.com/blog/il-8/

[Despe in reply to Kia17]

Good find, Kia! Most of them on our daily list.

[Kia17 in reply to Despe]

👍

[LAJ12345 in reply to Kia17]

Wow, good list, thanks!

[JerMan22 in reply to Kia17]

I remembered a few studies , including the first one below; a human study (n=1) of fisetin (one of those you list) on PD. It had some remarkable results:

liebertpub.com/doi/abs/10.1...

Example of others:

sciencedirect.com/science/a...

Search and you will find more. Fisetin is readily available and safe.

[chartist in reply to JerMan22]

JerMan22,

You are correct! looked at your links as well as others and Fisetin does meet the criteria to qualify for that list so I will add it to the list inside the original post to this thread! Thank you for the addition of Fisetin!

Art

[Kia17]

The following are IL-8 Increasers

Oxidative stress (specifically, H2O2) – but H2O2 inhibits IL-8 production in neutrophils

Sun/UVB + UVA

Exercise – small and only locally in muscle.

Obesity– IL-8 is released by fat cells.

Smoking

Estradiol – in breast tissue

Salmonella

Angiotensin II

Homocysteine

Supplements:

Lithium(in intestinal cells)

Resistant starch/Butyrate (intestinal cells)

Asian Ginseng (some parts)

[Dragona]

I find this extremely interesting, I don't understand all of it but really appreciate the time taken to post it and I will read it in small sections to understand it more, thank you so much😄

[Friend70]

Prednisone. They treat MS patients with prednisone, so why not PD patients (if the benefits outweigh the risks)?

[chartist in reply to Friend70]

Friend70,

It seems to me that I have seen a study where prednisone usage lessened your chances of getting PD, but prednisone comes with some common side effects which may be detrimental in PD. Weight gain is very common. Inability to fall asleep or stay asleep, a weakening of the immune system and it can have a negative impact on mood. These might make life more difficult for a PWP or anyone for that matter with long term usage. Getting good sleep is essential for better health.

Art

[bone60]

Thanks for the good information. I already take many of these supplements which may explain why I have been stable with minor symptoms for 3 years and negligible CD/Ld

[chartist in reply to bone60]

bone60,

That is very good to hear and know!

Art

[faridaro]

Brilliant post Art - thank you so much!!!

[bone60]

sildenafil also reduces IL-8

[chartist in reply to bone60]

bone60,

You are correct, Sildenafil is apparently an IL-8 inhibitor as outlined in this study :

ncbi.nlm.nih.gov/pmc/articl...

and it apparently crosses the BBB also as outlined here:

ncbi.nlm.nih.gov/pubmed/266...

I had originally intended to select from supplements and herbs for this purpose, but Sildenafil is so commonly used, I am going to add your suggestion to the list in the original post. Thank you!

Art

[LAJ12345 in reply to bone60]

Mmm, maybe it has the same pathways as horny goat weed’s icariin, as they have the same “other” effects.

[sharoncrayn]

" find ideas on how to potentially inhibit or antagonize IL-8 in an effort to reduce its very negative effects in promoting neuroinflammation and consequently neurodegeneration in PD since it is seldom mentioned or discussed, if at all, in regards to PD ..."

Ever wonder why?

Sharon

[chartist in reply to sharoncrayn]

Well, my feeling is that it makes more sense to target higher in the inflammatory cascade so that many of the inflammatory mediators that would normally become chronically activated and do their damage, would never even get the chance to do so. I think TNF-a biologics show the error of targeting lower in the inflammatory cascade as this introduces more and new problems. Chasing individual inflammatory mediators such as TNF-a, IL-1, IL-6 etc. seems like a very inefficient way of trying to control chronic inflammation wherever it is occurring in the body.

IL-8 being higher in the inflammatory cascade makes more sense to me and now seeing multiple ways to go after it seems to make even more sense to me. As of now, the studies are minimal, but it clearly seems that IL-8 should be a much more studied chemokine in PD and MS as well as many other diseases where IL-8 is a major bad player.

Being somewhat pessimistic and suspicious of the pharmaceutical industry because of the extreme amount of money involved in their products and because they are the ones funding many studies, I believe they could conceivably be working from the bottom up in terms of inflammatory mediators so that their future pipeline is pretty much full and guaranteed. So perhaps their thought process is let's start low with a TNF-a biologic inhibitor and when that product starts to lose popularity or develops side effect problems, we can just bring out another biologic that attacks another inflammatory mediator from the low end of the inflammatory cascade. Whereas, if they target higher in the inflammatory cascade to a chemokine like IL-8, they are potentially losing out on a lot of money makers in their pipeline. Money wise, their process seems to make plenty of sense, but health wise, too bad for us!

I guess this really makes me some kind of pessimist, but my experience makes me feel this is very possibly the case.

I realize that IL-8 plays a very important role in maintaining health, but it should mainly be in acute and temporary over activation. Chronic activation is detrimental and it would be helpful to have some options in trying to turn chronically elevated IL-8 levels down.

Art

[sharoncrayn]

"I guess this really makes me some kind of pessimist, but my experience makes me feel this is very possibly the case."

Your "experience" doing what in the cell biology field?

[chartist in reply to sharoncrayn]

When I said, "my experience" that was just to express what I have seen from the pharmaceutical industry, big business in general, the process by which drugs are brought to market and any time extraordinarily huge amounts of money are involved. I do not use the word greed, but it is possible that it is a major factor also. Every business pretty much wants to increase profits and the pharmaceutical industry is "definitely not an exception".

I do not mean to imply that the pharmaceutical industry is any worse than other huge industries, but the fact is they are a business first, with a bottom line of earning more and more money. One problem is to assume that just because they are medical companies, they are there for the purpose of making sick people better. That aspect often times has to take a back seat to profits! A major improvement to the industry as far as us end users go would be to stop allowing lobbyists who are essentially company representatives promoting bribery and should be illegal!

Art

[sharoncrayn]

Certainly influential but not unique...sitting at #5 in terms of Congressional lobby dollars.

Quoting from The Hill:

The five biggest spenders in lobbying last year (2018), in descending order, were the U.S. Chamber of Commerce, the National Association of Realtors, Blue Cross Blue Shield, the American Hospital Association and the Pharmaceutical Research & Manufacturers of America.

Rounding out the top 10 were the American Medical Association, Boeing, the National Association of Broadcasters, AT&T and Business Roundtable.

[chartist in reply to sharoncrayn]

Wow! I can see the potential on that list for a lot of conflict of interest and "legal bribery"!

Money in politics other than the offered salary should be illegal!If huge corporations are doing things on the up and up as they legally should, what is the need for lobbyist/bribe givers? I guess that is a self answering question!

Art

[chartist]

Curcumin is known to have very broad health effects and as might be expected, curcumin can cross the blood brain barrier (BBB) and can inhibit the chemokine IL-8 among many other inflammatory mediators associated with PD and MS according to the following :

ncbi.nlm.nih.gov/pubmed/122...

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

Judging from studies over the past five years or so, there are nanocurcumin and lypocurcumin formulations that purportedly are able to be even more effective at crossing the blood brain barrier.

Curcumin has shown benefit in so many studies including cancer, that it is no wonder it would end up on this list and again it has been discussed on this forum fairly regularly for its neuroprotective effects and other benefits!

Art

[LAJ12345]

The other thing my husband started a few weeks before the horny goat weed was the carnosine, recommended by a few on the site.

“Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation.”

ncbi.nlm.nih.gov/pubmed/183...

Can it cross the BBB?

ncbi.nlm.nih.gov/pmc/articl...

“Carnosine itself can also cross the BBB [18], ........”

So perhaps he has got lucky on this combination of new things!

[chartist in reply to LAJ12345]

Possibly so, a combination with synergy at inhibiting IL-8 and crossing the BBB! I will add carnosine to the list within the post.

Art

[chartist]

Another supplement that has been discussed on this forum, L-Theanine, for stress, relaxation without sedation and anxiety is another one that can cross the BBB and inhibit IL-8 according to the following. L-Theanine is derived from some mushrooms and green tea.

ncbi.nlm.nih.gov/pubmed/213...

mdlinx.com/internal-medicin...

I will add it to the list within the original post.

Art

[chartist]

In the original post I mentioned grape seed extract as a possible candidate to inhibit IL-8 and cross the BBB. In the following recent abstract (2019) it is found that not only the seed extract may be useful, but also the skin extract in terms of helping PD. It is only a PD mouse model study, but the benefits seem fairly clear!

ncbi.nlm.nih.gov/pubmed/311...

This study showed that grape seed and skin extract (GSSE) protected dopaminergic neurons and subsequent degeneration at multiple levels!

Art

[chartist]

EGCG from different colored teas is another supplement that has been discussed on this forum quite a bit and it also is able to cross the BBB as well as inhibit IL-8, IL-6 and TNF-alpha at a minimum. The following abstract confirms that EGCG inhibits IL-8 as well as other inflammatory mediators.

ncbi.nlm.nih.gov/pubmed/171...

The following study suggests that EGCG and some of its metabolites cross the BBB.

researchgate.net/publicatio...

One problem with EGCG is it has been noted for liver issues in some reports, but some of these reports are related to the use of EGCG as one component in dietary supplements which is a problem in itself. One obvious issue is that the other components of these dietary supplements is that any of the other components could also be a cause or it could be the combination of EGCG with any one of the other components that may be the problem. Another problem with diet supplements is that often times the people who are taking them are already overweight or possibly obese and this is why they are taking a relatively strong dietary supplement in the first place. It is common for overweight or obese individuals to potentially have existing liver issues and not necessarily even be aware that they have an existing liver condition and the total dietary supplement itself may exacerbate the liver condition.

Another possible cause for liver issues with EGCG is that EGCG is sometimes used as a supplement to fight various cancers, but under those circumstances there could be two potential problems. The first issue is that the cancer or standard cancer meds may have compromised the liver already and adding EGCG on top of it may compromise the liver further still. The second problem is that some people who believe that "more is better" may decide to dose EGCG at doses that are questionable at best because they are trying to fight cancer.

I have added EGCG to the growing list inside the original post. I'm still kind of surprised at how many on this list has been discussed on this forum quite often!

So if one chooses to use EGCG, then it seems prudent to include your doctor in that decision making process!

That way he/she can monitor your liver function if needed and make sure it is compatible with all that you are taking. Your pharmacist may be helpful in this area also because I have seen that doctors do not always know every contraindication for every drug.

Art

[silvestrov]

The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines.

"Co-injection of BA with CXC chemokine interleukin-8 (IL-8) into rat skin significantly inhibited IL-8 elicited neutrophil infiltration. BA did not directly compete with chemokines for binding to receptors, but rather acted through its selective binding to chemokine ligands."

ncbi.nlm.nih.gov/pubmed/109...

High quality baicalin is available through Liftmode. liftmode.com/baicalin-powde...

Note: From a Russian study baicalin should not be taken with vitamin C or NAC - N-acetylcysteine.

researchgate.net/publicatio...

[chartist in reply to silvestrov]

silvestrov,

Thank you for this one!

I will add it to the list within the original post.

Art

[bepo]

Thank you for posting this. I saved the post.

I have read about MS being an autoimmune disease. I have also read that many times MS is misdiagnosed and can be Lyme. Lyme Disease is way under diagnosed and is epidemic from what I have read. There is a MD, Terry Wahls, who has written books on how to cure MS through diet, etc. She was the guinea pig.

Could it be that some PD patients have Lyme as the cause?

[chartist in reply to bepo]

bepo,

It has been discussed several times on this forum on the idea that PD is sometimes actually LD because LD can mimic certain PD symptoms and at least one forum member has reported having LD and PD simultaneously.

I think the problem is that there is not a completely definitive method to accurately diagnose PD and then if you happen to live in one of the many parts of the country where LD is not that common, doctors are not well versed in the diagnosis of LD nor of the co-infections that can occur in conjunction with LD as well as the fact that LD can mimic other disease states such as Fibromyalgia, MS or Chronic Fatigue Syndrome.

I have read of a person who claims to have cured his wife of MS using colloidal silver(CS) and 2 or 3 other supplements, but that is only an anecdotal report and there are no studies to confirm efficacy, but being a person who makes and uses colloidal silver nanoparticles(AgNPs), I am open to that idea. I have seen AgNPs keep an HIV person alive for two years during a period when this person had no insurance to cover an HIV cocktail.

Given the above, it is somewhat understandable why the two can often be confused or completely misdiagnosed.

Art

[bepo in reply to chartist]

Thanks, Art.

I am a newbie on this site. I should have researched Lyme first.

We have a woman who lives in our small town, who has had Lyme for 60 years. It effects her heart, breathing, pain levels, etc. She was greatly helped with ozone saunas and autohemotherapy, but got a herxheimer reaction that lasted 2 weeks. She didn't return. I don't know if she knows who she would be without lyme.

[chartist in reply to bepo]

Yes, unless you live in an area such as Pennsylvania, where doctors are much more familiar with the disease due to its relatively high prevalence because of deer ticks in those areas, it can be a tough road with multiple misdiagnosis to further confuse the issue. Doctors who are very familiar with the disease also know that certain labs seem to be more accurate at identifying LD as well as its potential multiple co-infections and can request that the lab test for these co-infections which can have overlapping symptoms and are sometimes not initially apparent until later in the disease process.

I imagine that it is possible that LD can speed up disease progression in people who also have PD. This could likely be because LD adds to the total inflammatory burden as well as the total oxidative stress levels, both of which are at elevated levels in both diseases and can cause a decrease in total antioxidant capacity which will possibly further increase the disease status and progression in these patients.

Here is a map that gives an idea of places you are more likely to encounter the disease/deer tick carriers, but do not be fooled, the disease can be caught pretty much anywhere in the USA. There are similar maps available for other countries.

cdc.gov/lyme/datasurveillan...

Scroll down for individual states and scroll down further to the bottom map for a better view of the country as a whole.

Art

[chartist]

I am going to add Hesperidin and Hesperitin to the list of IL-8 inhibitors that cross the blood brain barrier, on to the list inside the original post above.

Hesperidin comes from the whitish pulpy matter between the skin and the fruit of citrus fruits such as sweet oranges, lemons and tangelos. Hesperidin has similar health qualities to Amla. It is abundant and inexpensive. It has antiinflammatory, antioxidant, antidiabetic and anti diabetic neuropathy qualities among others. Hesperidin has a very good safety profile. I use it and have used it at high dose with no apparent side effects. The following study abstracts suggests that it is an IL-8 inhibitor :

ncbi.nlm.nih.gov/pubmed/174...

ncbi.nlm.nih.gov/pubmed/176...

The following abstracts suggests that hesperidin and its flavanone-glycoside, hesperitin crosses the blood brain barrier and hesperitin has very similar effects to hesperidin. The following abstracts suggests that hesperitin and hesperidin crosses the blood brain barrier :

ncbi.nlm.nih.gov/pubmed/253...

ncbi.nlm.nih.gov/pubmed/222...

ncbi.nlm.nih.gov/pubmed/263...

Art

[JerMan22]

This is great, but let's not forget the power of diet and lifestyle changes.

youtu.be/NM_YOiJ0Mks(Not working as expected?)

youtu.be/u-HNoOdJInk(Not working as expected?)

[Coling]

great article - I think that you are onto something. I am interested in your mention about elevated levels of IL-8 found in the brain but not the rest of the body. you said referring to supplements 'we know that they all have two other very important activities of crossing the BBB and inhibiting IL-8" .... I may have missed it but can you point me to evidence that the supplements (in particular B1) can cross the BBB? many thanks

[chartist in reply to Coling]

Links to all of the information are in the original post and links to what everyone reported is in the replies.

Here is a link that specifically says that B1 crosses the BBB :

ncbi.nlm.nih.gov/books/NBK4...

Here is a direct quote from the B1 review :

>>> ' It can cross the blood-brain barrier. ' <<<

You should keep in mind that based on the video, inhibition of IL-8 is downstream from IL-17, so that may be the better target of the two, but targeting both by something that also crosses the BBB may be most useful! Thiamine does all three as does Melatonin, among its many many attributes. Melatonin and B1 seem likely to be synergistic imo.

Art

[Coling]

Fantastic many thanks Art.

[Bolt_Upright]

Awesome post Art! Do you have a recommendation on daily vitamin D dosing please?

[chartist in reply to Bolt_Upright]

Bolt,

I once read an article by a vitamin D researcher in which she suggested 8,000 mg/day as a dose that would not likely get you into trouble, but should be able to get most people well into the reference range (30 ~ 100 ng/ml). For some people that can push them right up to the top end of the reference range while for others it may only get them above the bottom of the reference range.

If you are specifically trying to treat something in particular, it may require going above the reference range or it may require that you stay below a specific level within the reference range and either way you should be monitored by a doctor who is testing your 25 OH d level regularly to insure you get where you are headed because of the high interindividual variability in where a specific dose may get your 25 OH d level to.

Art

[Bolt_Upright in reply to chartist]

Thanks Art. I was reading today how people with hashimoto's should be taking vitamin D and then saw it on this list also. Thinking of adding the l-theanine too.

Thanks!