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The Role of Cytokines In Autoimmune Thyroid Conditions

Cytokines play an important role in the pathogenesis of conditions such as Graves’ Disease and Hashimoto’s Thyroiditis. But what exactly are cytokines? They are similar to hormones, and some sources actually classify them as a type of hormone. Either way, cytokines are immunomodulating proteins, peptides, or glycoproteins that are involved in cellular communication (1) [1]. They are regulators of host responses to infection, immune responses, inflammation, and trauma (2) [2].

Certain cytokines play a pro-inflammatory role in autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis. In other words, these cytokines promote inflammation. Two examples of pro-inflammatory cytokines include Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α). However, there are also anti-inflammatory cytokines, as these cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response (3) [3].

What Role Do Cytokines Play In Autoimmunity?

There is considerable evidence implicating that the actual destruction of thyroid cells in autoimmune thyroid conditions may be caused by different and multiple mechanisms, including auto reactive T-lymphocytes, natural killer cells, and cytokines (4) [4]. The most significant factor that is likely to be involved in the induction of autoimmunity is a defect or deficiency in the immune regulation, particularly a disturbance in the balance between the effector T cells and regulatory T cells that prevent the development of autoimmunity (4) [4]. In other words, dysregulation of cytokine production can play a big role in the development of autoimmune thyroid conditions.

Some people reading this are familiar with the Th1 and Th2 pathways. Each of these pathways consist of different cytokines. The Th1 pathway consists of T-Helper cells which include the cytokines IL-2, IFN-γ, and tumor necrosis factor-α (TNF-α) (4) [4]. The Th2 pathway consists of B cells, and is characterized by the secretion of IL-4, IL-5, IL-6, IL-10, and IL-13 (4) [4]. High amounts of Th1 cytokines are commonly found in Hashimoto’s Thyroiditis (5) [5], and thus Hashimoto’s is typically known as a Th1-dominant condition. Graves’ Disease is thought to be a Th2-dominant autoimmune condition (6) [6].

Using Nutrients and Herbs To Balance The Th1 and Th2 Pathways Is Controversial

Some natural healthcare professionals will focus on balancing the Th1 and Th2 pathways. In other words, they will order a blood test to look for the presence of different cytokines in an attempt to determine if their patient is Th1 or Th2 dominant, and then give specific supplements or herbs depending on whether the person is Th1 or Th2 dominant. For example, if someone is Th1 dominant, they will recommend specific supplements and/or herbs to help stimulate the Th2 pathway. Similarly, if someone has a Th2-dominant condition they will do things in an attempt to stimulate the Th1 pathway.

You ideally don’t want to give anything that will stimulate the same pathway the person is dominant in. For example, the herb Echinacea supposedly stimulates the Th1 pathway, and thus shouldn’t be taken by someone who is Th1 dominant. And since most people with Hashimoto’s Thyroiditis are Th1 dominant, this would suggest that most people with this condition should avoid Echinacea. Studies do in fact show that Echinacea does affect the Th1/Th2 balance (7) [7], although this doesn’t mean that everyone who has a Th1 dominant condition needs to avoid Echinacea. While some people don’t do well when taking Echinacea, other people with Hashimoto’s Thyroiditis do fine when taking this herb. In any case, there is controversy over using nutrients and herbs to balance the Th1 and Th2 pathways, and for more information I would consider reading a journal article written by Dr. Parris Kidd entitled “Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease [8]“.

Understanding Nuclear Factor Kappa B

Nuclear Factor Kappa B (NF-kB) is a transcription factor, and activation of NF-kB is associated with pro-inflammatory cytokines such as IL-1 and TNF alpha. In other words, when an autoimmune response is triggered, the immune system will activate pro-inflammatory cytokines, which in turn will activate NF-kB. This in turn will contribute to the inflammatory process. Some studies suggest that NF-κB can also have anti-inflammatory roles by directly inhibiting expression of pro-inflammatory genes and by manipulating the expression or activity of anti-inflammatory cytokines such as IL-10 (8) [9].

NF-kB has often been referred to as a central mediator of the immune response, since a large variety of bacteria and viruses can lead to the activation of NF-kB (9) [10]. Some studies have shown that NF-kB may function more generally as a central regulator of stress responses, since different stressful conditions, including physical stress, oxidative stress, and exposure to certain chemicals, also lead to NF-kB activation (9) [10]. What’s important to understand is that the activation of NF-kB is a normal process, but it’s the chronic activation of this transcription factor which leads to problems.

Downregulating NF-kB Is An Important Factor In Restoring One’s Health

When someone has an autoimmune thyroid condition, one of the goals is to do things which will help to downregulate NF-kB. While the pharmaceutical industry focuses on developing anti-inflammatory drugs which inhibit NF-kB, there are natural supplements and herbs which have been proven to accomplish this and don’t come with the potential side effects of these drugs. I’ve discussed these supplements and herbs in different articles and blog posts, but let’s take a look at them again:

Turmeric. I think turmeric is a wonderful herb, as there are many clinical trials involving this herb, and you can read about many of the benefits in a separate article I wrote entitled “Turmeric and Thyroid Health [11]“. While I frequently recommend this herb to help with inflammation and to downregulate NF-kb, there are many other benefits this herb has to offer.

Resveratrol. I also like resveratrol a lot, and just like turmeric, I have written a separate article entitled “Can Resveratrol Benefit People With Graves’ Disease and Hashimoto’s Thyroiditis? [12]“. Resveratrol also has the ability to help with inflammation and can downregulate NF-kb.

Omega 3 Fatty Acids. Higher doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can also help with inflammation and downregulate pro-inflammatory cytokines (10) [13] (11) [14]. I recommend omega 3 fatty acids to just about all of my patients, usually in the form of fish oil supplements. Vegetarian sources such as flax oil and chia seeds can also be good sources of omega 3 fatty acids, although some people have difficulty converting alpha-linolenic acid into DHA and EPA.

Borage oil, Black Currant Seed oil, and Evening Primrose oil. These are all forms of gamma-linolenic acid (GLA), and can also help with inflammation and reduce the production of pro-inflammatory cytokines (12) [15] (13) [16].

Vitamin D3. I’ve spoken about the benefits of vitamin D in numerous articles and blog posts. Vitamin D plays a huge role in controlling inflammation, and unfortunately most people I work with are deficient in vitamin D. This is true even for many people who live in sunny areas. Of course not everyone is deficient in vitamin D, but the only way to know for certain is through testing, and I recommend for just about everyone with a thyroid or autoimmune thyroid condition to have their vitamin D levels tested.

Ginger. I don’t speak about this herb too much, although there is evidence that ginger may act as an anti-cancer and anti-inflammatory agent by blocking the activation of NF-kB through the suppression of the pro-inflammatory cytokine TNF-alpha (14) [17] (15) [18]. I suppose I’ll need to work on a future article entitled “Ginger and Thyroid Health”!

There are other agents which have the ability to downregulate NF-kb and pro-inflammatory cytokines, but these are some of the more researched ones. And of course I’m not suggesting that those people with an autoimmune thyroid condition such as Graves’ Disease or Hashimoto’s Thyroiditis need to supplement with all of these. In just about all people I will recommend omega 3 fatty acids (usually in the form of fish oils), a source of GLA, and to supplement with vitamin D3 if someone has a deficiency. It also can be beneficial to include turmeric and/or ginger as part of one’s diet, or in some cases to take a supplement consisting of these herbs. In any case, hopefully you now have a better understanding as to what cytokines are, and what role they play in autoimmunity.