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Hashimoto’s: What Is Going On With The Immune System?


Interleukin 18; An Immune Protein That Causes Inflammation in Hashimoto’s

Hashimoto’s is the most common autoimmune disease in the United States, but very few doctors, alternative practitioners or patients understand what is happening to the immune system or what to do about it.

As a result, treatment largely ignores the autoimmune part of the disease. In this post, I break down the basics of the immune system, explain how it affects people with Hashimoto’s and why it matters.

The Immune System Is Supposed to Protect Us

The immune system protects us from foreign invaders. Its like our body’s military. It finds the bad guys (like bacteria, fungus, parasites and viruses) and it kills them. It also cleans things up by destroying our own dead and dying cells. This is called cellular apoptosis, and if this process stops working, cancer develops.

In addition, the immune system creates inflammation as part of the process of healing after an injury. Recent research has shown that immune system has the ability to communicate with the nervous system, the endocrine system and digestive system and that it is actively modulating and influencing the body all the time.

The Immune System Has Different Parts

The immune system has many different parts, but the 2 important parts are called non-specific and specific immunity.

Non-Specific Immunity

The non-specific immune system is our immediate attack response. These are the front line soldiers that hang out in our borders (the mucous membranes of our lungs, digestive tract, skin and brain) and kill invaders.

This part of our immune system is called the T-Helper 1 (or TH-1) response. These are the macrophages (the Pac-man cells) and Killer T cells, the elite squads that are pathogen killing machines.

TH-1 is also broken down into messenger proteins like Interleukin-12 (IL 12), Interleukin 2 (IL-2), Interferon Gamma (IFN) and Tumor Necrosis Factor (TNF). These are the bad ass cells that get the job done.

IL-12 is a commander and facilitator that is responsible for helping cytotoxic lymphocytes, natural killer cells mature and it also supplies growth factor to help certain cells grow into the killers that they are.

It is also involved in turning on genes that result in attacks on specific organs and has been implicated as an important player in Hashimoto’s.

IL-2 is synthesized by CD 4 T cells, it increases antibody production, improves bone marrow responses to other immune cells and is used in the treatment of HIV.

A close relative of IL-2, IL-15, has been shown to be low in Hashimoto’s and treatment with levothyroxine increases IL-15 levels, as do some Chinese herbs.

Here is a perfect example of the contradictory nature of the immune system. Increasing IL-15, some theorize, may reduce the destruction of thyroid cells in Hashimoto’s.

Interferon Gamma is another commander that fights viruses and prevents their RNA from passing on genetic information, it activates the pacman cells (macrophages) to destroy organisms that get inside of cells and it kills tumor cells.

Tumor Necrosis Factor (alpha) also kills tumor cells, it turns on angiogenesis (the hallmark of malignant tumors), promotes fibroblasts and is involved in wound healing.

TNF (beta) is another commander who helps kill tumor cells, activates genes, and it helps instruct CD8 T cells, NK cells, and helper-killer T cells to induce them to fatally injure their targets.

A TNF receptor called CD95, which is responsible for cell death, has been found to be very high in patients with Hashimoto’s.

Specific Immunity

The specific immune system produces antibodies that label the bad guys. This part of the immune system is like the C.I.A., it gathers intelligence on the invaders and it labels them with an antibody. Once a foreign invader has been labeled by an antibody, its much easier for the killer cells to destroy it.

And like the C.I.A., it takes a while for them to gather the intelligence, so this process is usually delayed for a period of time. This part of the immune system is called T-Helper 2 (or TH-2).

These cells also do more than just labeling, they also attach themselves to certain cells like viruses to keep them from entering into our cells. This is important because once they are in our cells, they are much harder to kill and they can replicate more quickly.

TH-2 is also broken down into interleukins. The proteins IL-10 and IL-4 being 2 important ones.

IL-10 has been implicated in numerous autoimmune disease such as type I diabetes and multiple sclerosis. But it is another perfect example of the unpredictability of the immune system. It turns on some immune functions and shuts off others. It can block IL-1, IL-6 and TNF alpha, but turns on IL-2 and IL-4.

IL-4 is produced by CD 4 T cells and activates IgE, an immunoglobin important for creating immunity to parasites and involved in allergies.

Complicated, But Really Cool

To further complicate matters we have other parts of the immune system driving the immune attack and this is the family of interleukins that belong to IL-1. IL-1 is released by the pacman cells that are the front line attackers.

IL-18 belongs in this family of proteins and there is a lot of it in Hashimoto’s patients, especially those with severe symptoms that don’t respond to levothyroxine treatment. It may be responsible for severe inflammation.

Both parts of the immune system are needed for certain types of invaders. For example, viruses are often very small and can sneak past the border security. Then the TH-2 system uses it’s cellular informants to sniff them out and it tags them.

This can take several days to initiate and this is why it takes most people a few days to fight the common cold, which is caused by a virus.

In a general sense, the TH-1 system is considered inflammatory and the TH-2 system is considered anti-inflammatory. But in reality, they are both involved in the process of inflammation. And IL-12 and IL-18 are important drivers of inflammation in Hashimoto’s.

New Research Has Revealed Other Parts of The Immune System

Recent research has shown that there are other parts of the immune system that play important roles in this process. T-Helper 3 (TH-3) cells are the regulatory part of the immune system. They help to orchestrate TH-1 and TH-2 cells and act as kind of cellular general to call off or calm the attack.

T-Helper 17 (TH-17) cells are instigators and they rev up the attack and can make the damage and the carnage much more intense. A delicate balance of all parts of the immune system is important and with an autoimmune disease, like Hashimoto’s, this balance is lost.

What Happens with Hashimoto’s?

There are many possible reasons for the immune system to start labeling the thyroid as foreign tissue and create autoimmune thyroid conditions (including genetics, environment, endocrine imbalance, chemical exposure, responses to viruses and other antigens, stress responses and more).

It is probably some combination of those many factors that lead to the loss of self tolerance and the immune system attacking the body’s own tissue.

In most cases of Hashimoto’s, some combination of the factors mentioned above lead to a slow, gradual attack against the thyroid. This eventually leads to the loss of enough thyroid cells that the condition presents as primary hypothyroidism and is seen on a blood test as high TSH.

TSH becomes high because, when the thyroid is not working properly, the pituitary gland increases production of TSH to increase thyroid gland activity. For most people with Hashimoto’s, the thyroid never develops overactive symptoms. Over time, they develop symptoms of low thyroid function and get put on thyroid replacement hormone.

The issue of the autoimmune attack is never addressed. Instead, they are considered to be properly managed by having normalized TSH.

In a sense, these patients are having their TSH managed, but they are not managing the underlying problem. Over time, they lose more and more thyroid cells and they need more thyroid replacement hormone.

The result, for many people, is that they continue to have all the hypothyroid symptoms (like fatigue, hair loss, depression, constipation, cold hands and feet, etc.) because the root cause has been largely ignored.

What Is Going On with the Immune System with Hashimoto’s?

Since the thyroid is being destroyed, there is less thyroid hormone production. The immune system needs thyroid hormones to modulate TH-1 and TH-2 activity, so when this happens, the immune system can short circuit.

This leads to a larger number of TH cells, and autoantibody producing B cells. These cells accumulate in the thyroid and kill thyroid cells.

There are many possible scenarios that can lead to this outcome. For example:

In his book, Why Do I Still Have Thyroid Symptoms When My Lab Tests Are Normal, Dr. Datis Kharrazian gives some examples of things that can cause this:

* The T suppressor cells that regulate the immune response could be too few in number, and like a weak general that has lost control of his troops, this can lead to unchecked attacks by the immune system. And tissue like the thyroid becomes a casualty.

* TH-1 has a number of different soldiers, known as interleukins. These all have specific jobs. For example, interleukin 2 (IL-2) is a messenger chemical that sends out orders for the killer cells to start killing.

Some people make too much IL-2 and this creates a frenzy of destruction that can lead to the death of the thyroid cells. Chronic viral infections can cause too much IL-2 to be made and have been linked to the development of autoimmune thyroid disease.

* TH-2 also has lots of different soldiers. Interleukin 4 (IL-4) deploys B cells. Like some rouge C.I.A. agents, these cells can go crazy and tag the wrong proteins, and destruction of thyroid tissue is the result. Parasites and food allergies can cause too much IL-4 to be made.

* Too much sugar can cause the body to rapidly release insulin. These spikes in insulin can stimulate the production of too many B cells, they start tagging too many things, and this can lead to destruction of the thyroid.

And this is just the tip of the iceberg. In reality, there are many variables and many potential reasons for the immune system to short circuit. This is what makes treatment and management so challenging. And this is also why you must have a multi-pronged approach.

Which Parts of the Immune System are Out of Balance with Hashimoto’s?

In most cases of Hashimoto’s, researchers think TH-1 cells become overactive (but this is not true for everyone and is an oversimplification). It seems IL-18 and IL-12 also act together to throw a beating to the thyroid.

Look for development of drugs that inhibit these 2 interleukins. In the meantime, stay tuned to learn about herbs and foods that can accomplish that naturally!

Hashimoto’s people also often have a weak TH-3 regulatory system and their TH-2 may or may not be out of control. TH-17 is also often wound up, making the attack more intense. And none of this happens in a vacuum.

This is all taking place in the context of the body where the immune system is interacting with the endocrine system, the digestive system and the nervous system. Further complicating the task of unwinding this mess. Its no wonder patients and doctors alike get frustrated and overwhelmed.

Your Hashimoto’s Is Unlike Anyone Else’s

The reality is that your Hashimoto’s is not the same as anyone else’s. You may have an overactive TH-1 system or you may not. You may also have a weak TH-2 system or you may not. TH-3 is probably weak and TH-17 is also probably revved up.

And you may have leaky gut, and/or blood sugar issues, and/or adrenal fatigue, and/or anemia, and/or some active parasite or latent viral infection. It goes on and on.

You need an individualized approach that will create a unique action plan for your unique set of circumstances.

This is why I have created my 3 month program: Healing Hashimoto’s: The 5 Elements of Thyroid Health. In this program you will learn how to develop your own unique template for healing your Hashimoto’s and, most importantly, how to calm, balance and manage your immune system.

Here’s a video of a webinar I did called Introduction to the 5 Elements of Thyroid Health that you might enjoy.

In my next post, I will discuss how this is done and we’ll look at some real examples to see how all of these different pieces fit together.




Drugarin D. The pattern of Th1 cytokine in autoimmune thyroiditis. Immunol Letts, 2000; 71: 73-77

Risk factors for and prevalence of thyroid disorders in a cross sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clin Endocrinol (Oxf) 2003 Sep;59(3): 396-401


Autoimmune Disease and Chinese Medicine, M.M. Van Benschoten, O.M.D. 9/13/2003

Why Do I Still Have Thyroid Symptoms? When My Lab Tests Are Normal, Dr. Datis Kharrazian, DHSc., DC, MS, Morgan James Publishing, 2010, page 46

{ 16 comments… add one }
  • Sherry March 9, 2013, 3:39 pm

    I contacted Hashimoto’s 32 years ago, after I had my Son! I no longer have a thyroid and I am losing my hair and nails are bad!!

    • Marc Ryan March 11, 2013, 8:08 am

      Hi Sherry,

      Thanks for your comment. Pregnancy is one of the major factors in developing Hashimoto’s. I hope you are working with someone to help you manage your condition.


  • Dana Trentini March 11, 2013, 9:31 am

    Great article Marc. You’ve made what may be a complicated topic into something easy to understand and super helpful.

  • Jessica June 7, 2013, 4:58 am

    Hi Marc. Thank you for your article. I just wanted to clarify that the various IL’s, TNF, and IFN are not cells but proteins. 🙂

    • Marc Ryan June 7, 2013, 8:27 am

      Hi Jessica,

      Thanks for your comment. In most cases throughout the article, I have referred to them as proteins. But, as you rightly pointed out, I mistakenly referred to IL-18 as a cell in the caption under the image. I appreciate you taking the time to make me aware of it and I believe I have gotten it right in the rest of the blog post. Also, if you are knowledgable about this sort of thing and can point me to any research that may be helpful, I would greatly appreciate that as well.


  • Shweta Gupta June 17, 2013, 11:55 pm


    I am 30 year old and I have autoimmune hypothyroid for last 3 years.Though my TSH level is under control with medication,I feel scared to imagine my own body attacking itself.
    My doctors have told me its an irreversible condition but I am hoping there must be a solution.
    Please advice if anything could be done

    • Marc Ryan June 20, 2013, 9:37 am

      Hi Shweta,

      This is an irreversible condition, but that does not mean that nothing can be done. On the contrary, a lot can be done. Basically, you need to learn a new lifestyle that supports better management of your autoimmune condition. That’s what I help people learn how to do and I guide them to finding solutions so that they can live a full productive life with this disease. I offer a free 30 minute confidential consultation if you’d like to learn more. You can schedule by clicking on the button in the right column of my website on the home page.


  • Gayle Weber (@GW1965) October 31, 2013, 7:42 am

    Wow, another great article. Confirms why when being treated for my thyroiditis, I have more issues with stress and cold sores. Instead of catching the cold that goes around, I get a lovely cold sore. Crazy.

    • Marc Ryan October 31, 2013, 8:44 am

      Hi Gayle,

      Thank you for your kind words! I have also had issues with cold sores since I was a teenager. In times of stress and seasonal changes I used to get them like clock work. I get it. It is a tenacious virus.


  • Lisa November 1, 2013, 11:47 am

    Another great read Marc
    I have Hashi and four the past three weeks I been burning up like crazy red face , sweaty body that can last up to 20 min. and its on and off all day and its the first time it’s ever happened to me.
    They say expect the u expected

    • Marc Ryan November 1, 2013, 1:36 pm

      Hi Lisa,

      Thank you for your kind words! Yes, things can certainly happen unexpectedly. However, there is a way to eliminate many of the variables and figure out what your triggers are. That is the problem, the triggers. I don’t know if you are aware of it, but I offer a free 30 minute Hashimoto’s Healing Discovery Session. In it you can share with me where you are and where you want to be, I can make some suggestions that will help right away, and we can discuss how I might be able to help. If that interests you, please click on the button in the right column of the hoe page to schedule.

      Best, Marc

  • Lynette November 2, 2013, 9:25 am

    I had my thyroid removed 5 yrs ago after a major attack on it. Went from untreated hypo to hyper ( labs always within range) but they thought there was cancer ( ended up not). Also was dx with hashimotos. So my question is: does hashimotos still exist when thyroid has green removed? My tsh always normal on synthroid but still feel horrible almost everyday of my life. Is hashis still there?

    • Marc Ryan November 2, 2013, 10:44 am

      Hi Lynette,

      Thank you for reaching out. This is one of the most frequent questions I am asked. Here is my opinion on this issue. Any honest surgeon will tell you that they can’t remove all thyroid tissue. They must preserve nerves, major vessels, the parathyroid and lymph glands. So some thyroid tissue always remains. Furthermore, Hashimoto’s is an autoimmune disease. Autoimmune disease exists independent of the thyroid. The thyroid is just one particular tissue that is being attacked by this process.

      It is often the case that once you have one autoimmune disease the door is open to others, because you have already lost self-tolerance. So, in answer to your question, let me rephrase it. Is autoimmune disease still there? In my opinion, yes.

      Removing the target tissue does not remove the loss of self tolerance or the probability that other tissues will be attacked. So, for all intents and purposes, yes Hashimoto’s is still there. Or the process that gave rise to Hashimoto’s is still there. You should still behave and act as though you have autoimmune disease or risk further progression and other autoimmune diseases.

      Normal lab work is very common and testing TSH and T4 are problematic for many reasons and do not tell you anything about the underlying autoimmune disease. If you want to find out definitively, test for antibodies for other autoimmune diseases. I work with a lab called Cyrex labs that has a comprehensive test for about 25 different antibodies to various tissues in the body. That is a test that would give you a good sense of where you are in the progression of autoimmunity.


  • Lynette November 2, 2013, 12:32 pm

    Wow Marc, you explained it so well so thank you! And yes, my surgeon did say he left a small portion of the right side but called it total thyroidectomy. So thanks for explaining that as well. I’m assuming if I went to my dr to inquire about this comprehensive test for the antibodies, she would know what I’m referring to–or is there a special name for this test. I did just have my vit D tested and it was low so I have started on supplements for that. I’ve had others tell me their surgeon told them they will always need to take vit D and calcium for life, but my drs never mentioned anything about either of them. What is your thought on that? All I know is that everyday is a struggle. Fatigue and weight being the most unbearable! Any thoughts or suggestions, I truly appreciate. I had symptoms for years that the drs would never treat because my labs always normal and then one day, my system couldn’t take it anymore and that’s when I went into hyper state and literally felt like I was going to die everyday until they removed my thyroid which did correct those symptoms. So when a dr tells me even now that my labs are fine, i am more than skeptical. I know how I feel! Once again, any more input you have is beyond appreciated!!!