Is TH1/TH2 an outdated model?--TH17

[drob31]

I came across an interesting article by Dr. Peterson (David Peterson, DC, DCCN, FAAIM), who I actually got to talk to on the phone for an hour, and it appears to be useful, cutting-edge information.

"TH1/TH2 Challenge

When the activity of one subset goes up, it represses the activity of the other similar to a seesaw or teeter-totter. Some practitioners recommend the TH1/TH2 Challenge to determine if symptoms are immune related. In this test, one immune stimulating supplement is taken at a time and a journal is kept of the symptoms experienced. One supplement stimulates the TH1 side of the immune system, and the other supplement stimulates the TH2. The reactions to these supplements are used to determine which side of your immune system is out of balance. However, very few people are strictly TH1 or TH2."



"TH17

The purpose of Th17 cells is to clear pathogens, which are not efficiently handled by TH1 and TH2 type of immunity. The induction of Th17 responses must go through three distinct steps: Induction, amplification and stabilization. The stability of Th17 population is only relevant if it is protective against a given pathogen-invader or other kind of insult. If Th17 cells lose their stability they become highly proinflammatory and promote the destruction of your body’s tissues as occurs in autoimmune conditions. In essence, your immune system chooses to sacrifice body tissues by destroying in order to preserve the rest of your body.

The TH-1/TH-2 Challenge as noted in the book “Why Do I Still Have Thyroid Symptoms?” was printed prior to understanding of TH-17. The TH-1/TH-2 Challenge may provoke a TH-17 response. The TH-17 destroys tissue rather than allowing it to be inflamed; analogous to a suicide bomber attack that you can not defend against."



Source: http://livingwellnessblog.wordpress.com/2012/10/12/am-i-th1-or-th2-or-th17/

 

[Hip]

Profs Nora Chapman and Steven Tracy suggest that coxsackievirus B myocarditis infection may be a good model to study the coxsackievirus B infections found in many ME/CFS patients.

Now the Th17 mode has been found to worsen coxsackievirus B myocarditis.†

So it is possible that patients with coxsackievirus B-associated ME/CFS might benefit from Th17 inhibitors.



Th17 Inhibiting Drugs and Supplements:

N-acetyl-glucosamine inhibits Th1 and Th17 responses. 1
Propolis inhibits the differentiation of Th17 cells. 1
Green tea (EGCG) inhibits the differentiation of Th17 cells. 1
Ursolic acid (available as the supplement "Ursobolic") blocks stat3, and the inhibition of Stat3 activation blocks Th17 activation while promoting Th1 or cell mediated immune responses. 1
Zinc suppresses Th17 development via inhibition of STAT3 activation. 1
Vitamin D suppresses Th17 cytokine production. 1
Vitamin D plus a TNF inhibitor (eg: cat's claw or vinpocetine) will reduce Th17. 1
Vitamins A and D synergistically suppress the development of Th17 Cells. 1 2
Retinoic acid inhibits Th17. 1 Note that beta carotene a precursor to retinoic acid. 1
Baicalin inhibits Th17 cell differentiation. 1
Grape seed extract reduces Th17 / Treg ratio. 1
Cordyceps sinensis increases regulatory T cells to Th17 cell ratio. 1
Triptolide from the herb Tripterygium wilfordii inhibits the differentiation of Th17 cells. 1
Fucoxanthin (found in brown seaweed) induces regulatory T cells and inhibits Th17 cell differentiation in vitro. 1
Berberine suppresses Th1 and Th17 T cell differentiation in type 1 diabetic mice. 1
Olive leaf extract reduces IL-17 (and possibly therefore Th17). 1

Intermittent fasting might be helpful - it increases the amino acid starvation response (= amino acid response pathway, AAR), which then reduces Th17.
Restricting proline reduces Th17 cell differentiation. Foods highest in Proline

Interferon alpha down-regulates IL-17 expression and Th17 differentiation in vitro and in vivo. 1
Interferon beta inhibits human Th17. 1
Methylprednisolone has a suppressive effect on Th17 cells 1
Simvastatin inhibits IL-17 and Th17. 1
Etanercept downregulates the Th17 pathway. 1
Digoxin (from foxglove, Digitalis lanata) and its derivatives suppress Th17 cell differentiation. 1
Telmisartan inhibits Th17 differentiation. 1
Calcipotriol (vitamin D analogue) suppresses Th17. 1



Note: Candida albicans is a potent inducer of the Th17 response. 1

The Th17 response is important for fighting Candida albicans and Staphylococcus.

 

[Jonathan Edwards]

Is this an advert?

"Call today! 530-615-4083"

Mr Peterson seems to be a cranial osteopath and TH17 was cutting edge in 1999. I hate to be deflationary again but ...

 

[drob31]

Is this an advert?

"Call today! 530-615-4083"

Mr Peterson seems to be a cranial osteopath and TH17 was cutting edge in 1999. I hate to be deflationary again but ...

He's done allot of research with lectins. He believes lectins can elicit an autoimmune response. I'm not sure about TH17 though, but it seems like the focus is always on TH1/TH2, and TH17 is rarely mentioned.

 

[Jonathan Edwards]

He's done allot of research with lectins. He believes lectins can elicit an autoimmune response. I'm not sure about TH17 though, but it seems like the focus is always on TH1/TH2, and TH17 is rarely mentioned.

TH1/TH2 was the focus up until about 15 years ago. Since then immunologists have been talking about TH17 and Treg and very little else. To be honest I don't think Mr Peterson is an immunologist.

 

[drob31]

So you're saying TH1/TH2 is irrelevant? Oh, I know he isn't an immunologist, but he's researching in that area. I just see allot of people posting about TH1/TH2 and ways to modify it but not much mention of TH17 or anything else.

 

[Jonathan Edwards]

I was talking more about the trends in what immunologists like to talk about. I do personally think TH1 and TH2 and in fact TH17, are not very relevant to autoimmune disease, except possibly type 1 diabetes, because nobody has ever really shown anything wrong with T cells in human autoimmune disease. The reason for calling it autoimmunity is always the autoimmune B cells and nobody has been able to find autoimmune T cells as well. There was an assumption early on that they would be there but it never worked out that way. The only case where we know what the T cells are recognising is coeliac disease where they recognise a foreign protein - gluten/gliadin - not self.

Unfortunately 90% of immunological papers on TH subsets are written on mouse experiments that do not necessarily have anything to do with human disease. I don't know of any anti-T cell therapies that work in human autoimmune disease and there are lots of examples of failures.

 

[drob31]

This is some of Dr. Peterson's work on trying to find the connection between TH1/TH2/TH17 and hashimotos:

"Four Different Hashimoto Patients – Four Different Immune Responses

All had bad reactions with the Th1/TH2 challenge. Why? All have an overactive Th17 immune response. Three have a suppressed TH1 response. One has a suppressed TH2 response. The upper right is immunocompromised. The lower right is immune stimulated to everything. The lower left is a raw vegan over-consuming Soft and Hard Lectins. The upper left TH1 immune system collapses when exposed to bacteria driving straight into TH17."

 

[halcyon]

Would autoimmune T cells even hang around long enough to be found though? Especially by the time symptoms of autoimmunity would show up.

 

[Jonathan Edwards]

I am not sure why autoimmune T cells would be invisible. Getting samples of T cells from blood is easy enough. If they do not hang around then they would not be the reason for the continued autoantibody production over many years so presumably there must be another explanation anyway?

Most theories of autoimmunity that invoke T cells blame the T cells for directly causing the symptoms but if you take T cells out of RA joints that have been wrecked you cannot find much wrong with them. They seem to be activated by non-specific cytokine signals rather than antigen.

 

[Jonathan Edwards]

This is some of Dr. Peterson's work on trying to find the connection between TH1/TH2/TH17 and hashimotos:

Can you work out what these diagrams mean? I have never seen diagrams like that before. Aren't they just diagrams of ideas - they do not look like any sort of experiment result.

 

[drob31]

I believe it's an output from a test called: Neuroscience NEI Gold 5516

https://www.neurorelief.com/index.php?p=testDet&testID=200&TestPanelName=NEI Gold

Stimulated Cytokines (see profile 5082)

 

[Jonathan Edwards]

I believe it's an output from a test called: Neuroscience NEI Gold 5516

https://www.neurorelief.com/index.php?p=testDet&testID=200&TestPanelName=NEI Gold

Stimulated Cytokines (see profile 5082)

I don't think these are outputs from a test. There are no numbers, or even much indication what is being measured.

 

[halcyon]

I am not sure why autoimmune T cells would be invisible. Getting samples of T cells from blood is easy enough. If they do not hang around then they would not be the reason for the continued autoantibody production over many years so presumably there must be another explanation anyway?

Most theories of autoimmunity that invoke T cells blame the T cells for directly causing the symptoms but if you take T cells out of RA joints that have been wrecked you cannot find much wrong with them. They seem to be activated by non-specific cytokine signals rather than antigen.

I thought that plasma B cells hang around almost indefinitely and continue to produce antibodies without further stimulation from T lymphocytes?

 

[Jonathan Edwards]

I thought that plasma B cells hang around almost indefinitely and continue to produce antibodies without further stimulation from T lymphocytes?

A reasonable point, but not indefinitely. Our antibody titres against microbes wane after a decade or so - which is why we get tetanus boosters. And IgM plasma cells tend not to last very long and in autoimmunity IgM autoantibodies can go on being high for ever. Moreover, the fact that autoantibodies tend to disappear after rituximab treatment indicates that a good proportion of autoantibody plasma cells are rather short lived, for reasons we do not understand.

 

[adreno]

@Jonathan Edwards

So could having a bunch of vaccinations have any bearing on autoimmunity, since they increase antibodies?

 

[Jonathan Edwards]

@Jonathan Edwards

So could having a bunch of vaccinations have any bearing on autoimmunity, since they increase antibodies?

Vaccination does not increase the diversity of antibodies since this is due to random products of millions of types each day. Nor does it increase total antibody levels much. The bone marrow just shifts to making more of the antibodies that bind to the vaccine proteins. Although it is very popular to think that vaccines might trigger autoimmunity it does not add up to me. You can only get autoimmunity if the veto on autoantibody fails. If the veto fails then your own antigens are quite good enough to amplify selective antibody production. Vaccines might provide a danger signal but if that was all there was to it then farmers and trash collectors would constantly be getting autoimmunity from dirty skin wounds. And they don't.