Thyroid-Immune Crosstalk—Part 2: Thyroid Influence on Immunology

Thyroid Influence on Immunology

Thyroid hormones play critical roles in the differentiation, growth, and metabolism of immune system regulation.  Every single immune cell has receptor sites for thyroid hormone, including immune cells.  If a person is in a thyroid-deficient state, there has to be an effect on their immune response because thyroid hormones help influence their activity.  Immune cells require thyroid hormone for proper maturation and immune regulation and regulation of T and B cells.

 Inflammatory Modulation and Thyroid Hormones

How can people modulate autoimmune dysregulation if they are thyroid deficient?  Also, you cannot dampen autoimmunity if they are thyroid deficient.  One study found that thyroxine has the potential to dampen inflammatory cytokines such as IFN-gamma, IL-4, IL-10.  Increased cytokine activity means more inflammation, pain and destruction of tissue.

What is causing the receptor sites to not respond?  Cytokine load (the amount of cytokines and cytokine activity).

What does thyroid hormone essentially do?  Dampen cytokine activity.

It is very difficult to manage autoimmunity in a thyroid hormone deficiency state.

 We know that thyroid hormones have the ability to dampen cytokine load which has an impact on conversion of T4 to T3 and responsiveness of the receptor site.  We also know that inability to dampen inflammatory cytokine response leads to systemic inflammation.  So you can see a vicious cycle going on.  The autoimmunity increases cytokine load and the cytokine load has impacts on thyroid metabolism:

  • It can suppress TSH
  • It can cause decreased conversion
  • It can make the receptor sites less responsive

When people become thyroid deficient, they can’t modulate autoimmunity as well and they have less potential to dampen their cytokine activity, meaning more inflammation.

Thyroid and Intestinal Inflammation

We also know that thyroid hormones have major impacts on intestinal inflammation.  Thyroid hormones have powerful influences on the integrity of gastrointestinal mucosa tight junctions in both the stomach and small intestine.  Lack of thyroid hormone stimulation to gastric and intestinal cells leads to ulcerations  and intestinal permeability known as “leaky gut syndrome”.  When people are thyroid deficient, they are more prone to intestinal inflammation and intestinal permeability (leaky gut).

Both thyroxine (T4) and triiodothyronine (T3) have been shown to protect the intestinal mucosal lining from stress-induced ulcer formation.  Additionally, endoscopic examination of gastric ulcers found low T3, low T4 and abnormal  levels of RT3 on gastric ulcerative tissues. 

Long-term hypothyroid states lead to leaky guts

We know that people who are hypothyroid for a long period of time develop leaky guts.  They then develop more food allergies and chemical sensitivities and more autoimmunity.  One of the things you need to consider is that these people have gut permeability issues.  Even if they are taking thyroid hormone, they cannot get thyroid effects on their gut epithelium to calm down the inflammation if they have thyroid resistance.  The fact that they have thyroid resistance prevents them from getting the inflammatory-calming effects of thyroid hormone.  So what do they end up with?  Leaky guts. 

Most hypothyrioid patients are gluten sensitive

Even if they are on thyroid hormone, if they have inflammation and increased cytokine load, this cytokine load will prevent thyroid hormone from having an effect on the receptor sites.  The overlapping thing with these Hashimoto’s patients is almost all of them have gluten sensitivity.   Some of them have full-blown Celiac’s disease. 

Hypothyroid patients have:

  • gluten sensitivity that destroys their gut
  • intestinal cells that are not responding to thyroid hormone
  • cytokine surges

 So they end up with leaky guts

Hypothyroid patients have leaky gut susceptibilities for the rest of their life

Intestinal permeability is part of their condition and the will have this susceptibility for the rest of their life.  Based on the physiology of their condition, they will always be susceptible to a leaky gut.  There will be times when they get stressed out and get worse, when they eat certain food for example.  They have to know how to deal with it and they have to have a strategy to work through this during this period of time.

Our goal with hypothyroid patients is to empower them to understand their condition and how to better cope with it.  There will be times when their gut permeability improves and they are less symptomatic and there will be times when it gets worse.   They have to understand that they are prone to developing leaky gut for the rest of their life.

TH1/TH2 Dysregulation and Hypothyroidism

When patients are thyroid deficient, they are at increased risk of TH1/TH2 dysregulation.  Thyroid hormones modulate CD4 and CD8 activity and TH1 and TH2 responses.  These expressions influence the potential to regulate abnormal autoimmune expression.   

 Most hypothyroid patients are autoimmune and most have:

Decreased thyroid hormone production which leads to:

  • Immune dysregulation
  • Increased inflammatory cytokines
  • Leaky gut syndrome

When these hypothyroid patients are managed by practitioners from a single nutrient or drug model, they don’t get very far with them.  They need to have a person that understands the complexity of the condition and manage them for it and teach them what it is and empower them so they can manage it themselves.   

Unique characteristics of hypothyroid patients

There are a couple things that are very unique about these hypothyroid patients:

  • They shift into a TH1 or TH2 polarity and this will never change
  • There are certain supplements that can flare them up, depending on their dominant side, or you can calm down their autoimmunity by giving them supplements from their non-dominant side
  • We can expect that these people will have limited response to thyroid hormone but they still need it since if they don’t have the thyroid hormones, they can’t dampen the autoimmunity

We can expect them to do better with a T3 source of thyroid hormone because they often have conversion problems but on the other hand, when they have flare-ups and unremitting attacks, they have excess T3 in their system, so they cannot tolerate anymore T3.

The hypothyroid-gluten sensitivity connection

The genotype for Hashimoto’s and the genotype for gluten sensitivity are the same.  You can expect almost all these people to have both.  They will have gluten sensitivity, intestinal permeability and cytokine surge issues.

You will have the most clinical effect if you can:

  • Dampen TH1/TH2 responses
  • Get them off gluten
  • Improve intestinal permeability
  • Decrease cytokine load

 Summary of Thyroid Influence on Immunology

Thyroid hormones:

  • produce a protective influence on the intestinal lining
  • increase the proliferation of intestinal intraepithelial lymphocytes to improve the intestinal barrier system
  • modulate the expression of intestinal inflammation
  • increase intestinal catecholamines and enhance intestinal blood flow
  • enhance T-helper stimulation of nitric oxide synthase
  • modulate immune cell cytokine release
  • modulate lymphocyte subpopulation in mediating inflammation
  • modulate dampening of excess inflammatory cytokine responses in inflammatory states
  • modulate immune cell homeostasis apoptosis

Article by Datis Kharrazzian, D.C., Mastering the Thyroid, Nov. 12, 2010