Should You Get Tested For Cytokines?

I’ve spoken about cytokines in past articles and blog posts, as these are proteins that play a role in regulating the inflammatory process.  Although pro-inflammatory cytokines play a role in autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis, there are also anti-inflammatory cytokines as well.  Some healthcare professionals will test the cytokines of their patients, and in this blog post I’ll discuss if this is something everyone with an autoimmune thyroid condition should do.

Rather than beat around the bush, let’s jump right into the main subject and talk about testing for cytokines.  So why do some healthcare professionals choose to test the cytokines of their patients?  After all, assuming this isn’t covered by your health insurance, testing for cytokines can be expensive, and so what purpose is served by testing these?  Well, the main reason why healthcare professionals choose to do this type of testing is in order to modulate the Th1 and Th2 pathways.  I’ve spoken about this in previous articles and blog posts, but I’ll briefly talk about this below.

What You Should Know About Th1 and Th2

T helper cells are one of the most important cells related to immune system health…specifically something called adaptive immunity.  They help to activate B cells, which in turn secrete antibodies, and they also activate other T cells to help kill infected cells.  However, these T helper cells first need to be activated, and once activated they will differentiate into Th1 or Th2 cells. These cells have different functions, and they will secrete different cytokines.  There are other types of T helper cells, but I’m going to mainly focus on the Th1 and Th2 cells here.

Autoimmunity involves an imbalance of these Th1 and Th2 cells.  Conditions such as Hashimoto’s Thyroiditis are typically considered to be “Th1 dominant”, which means that there is an excessive amount of Th1 cells.  On the other hand, most cases of Graves’ Disease are considered to be “Th2 dominant”, where there is an excessive amount of Th2 cells.  However, this isn’t set in stone, and the only way to know for certain whether someone is Th1 dominant or Th2 dominant is to test the cytokines.

But what does someone do with the information they receive after testing for cytokines?  Well, there are some studies which show that certain nutrients and herbs can help to stimulate Th1 cells, while other nutrients and herbs can stimulate Th2 cells.  And so for example, if a doctor is working with someone who has Hashimoto’s and does cytokine testing, and this shows that the person is Th1 dominant (has an excess of Th1 cells), then this doctor might recommend nutrients and herbs that stimulate the opposite pathway (Th2), while at the same time tell the patient to avoid nutrients and herbs that stimulate Th1 cells.

What Is Nuclear Factor Kappa B?

Inflammation involves numerous signaling pathways which involve the regulation of both pro- and anti-inflammatory cytokines.  Nuclear Factor Kappa B (NFkB) is a transcription factor that plays an important role in helping to regulate inflammation.  The activation of NFkB is a normal process, but with autoimmune conditions what happens is that NFkB becomes chronically activated, which makes it more challenging to control the inflammation.  And when dealing with autoimmune thyroid conditions such as Graves’ Disease and Hashimoto’s Thyroiditis, one of the primary goals should be to downregulate NFkB, which can be accomplished through the use of certain nutrients and herbs.

The Flaws With Trying To Balance The Th1 and Th2 Pathways

Using nutrients and herbs to balance the Th1 and Th2 pathways might sound like a good idea, but there are flaws to taking this approach.  For example, some sources label turmeric and resveratrol as stimulating the Th2 pathway, which should suggest that they should be avoided in people with Th2 dominant conditions, including Graves’ Disease.  However, other sources show that these can inhibit both Th1 and Th2 cytokines (1), and both turmeric and resveratrol also help to increase regulatory T cells and decrease Th17 cells, which can suppress autoimmunity.  Over the years I’ve had many of my patients with Graves’ Disease take turmeric and/or resveratrol without having a negative effect on their recovery.

Another example involves the herb Echinacea, which can stimulate the Th1 pathway, and thus might be problematic for those with Th1 dominant conditions, including Hashimoto’s Thyroiditis.  I will admit that I don’t give Echinacea often to my Hashimoto’s patients, although it’s not necessarily because I’m fearful of this herb worsening their condition.  There are a few well known and competent healthcare professionals who willingly give Echinacea to their patients with Hashimoto’s Thyroiditis, and they claim that this usually doesn’t cause any negative effects on their health.  Master herbalist Kerry Bone, who is the author of a few textbooks on herbal medicine, doesn’t seem to be concerned about Echinacea worsening a condition such as Hashimoto’s.  Not too long ago I attended a seminar conducted by Ronda Nelson, who has many years of experience working with Hashimoto’s Thyroiditis and other endocrine conditions, and she recommends Echinacea to many of her patients with Hashimoto’s Thyroiditis.

I’m not suggesting that there isn’t any validity to the Th1/Th2 balancing theory, as I have come across patients with both Graves’ Disease and Hashimoto’s Thyroiditis who didn’t do well when taking certain nutrients and herbs.  This doesn’t mean that it was due to the agent stimulating the Th1 or Th2 pathway, although perhaps this was the case.  Without question this remains a controversial topic.

How Do You Test For Cytokines?

There are a few labs that offer cytokine panels.  True Health Labs and Life Extension are two companies I know of that offer testing for cytokines.  If anybody reading this is familiar with other companies which offer cytokine testing please feel free to post the name of the company/lab in the comments section below.

Th1 vs. Th2 Cytokines

What I’d like to do here is present a list of some of the more well known cytokines associated with the Th1 and Th2 pathways:

Th1 Cytokines:

Tumor necrosis factor (TNF) alpha

Interferon gamma (IFN-y)

Interleukin (IL)-2

IL-12

IL-18

Th2 Cytokines:

IL-4

IL-5

IL-6

IL-9

IL-10

IL-13

How Do You Inhibit These Cytokines?

From a conventional medical standpoint, selective cytokine inhibitory drugs are one option.  There are also TNF-alpha inhibitors, which specifically bind to and inhibit the cytokine TNF-alpha.  However, non-steroidal anti-inflammatory drugs (NSAIDs) can also inhibit cytokines.  Of course these drugs come with potential side effects, and one reason is because you don’t want to completely inhibit these pathways.  The real goal is to address the cause of the problem while trying to do things to reduce, or downregulate pro-inflammatory cytokines.

Fortunately, there are nutrients and herbs which can help to accomplish this, and these are some of the more well-researched ones:

Turmeric.  There is plenty of evidence which shows that turmeric can help to inhibit NFkB and reduce proinflammatory cytokines (2) (3) (4), and it also can help to increase regulatory T cells while decreasing Th17 cells (5).

Resveratrol.  Like turmeric, resveratrol can also inhibit NFkB and result in a decrease in proinflammatory cytokines (6) (7) (8).  In addition, it can help to regulate the Treg/Th17 balance (9) (10).

Omega 3 fatty acids. Numerous studies show that omega 3 fatty acids in the form of fish oils can decrease pro-inflammatory cytokines, while increasing anti-inflammatory cytokines (11) (12) (13).

Vitamin D3.  There is evidence that a vitamin D deficiency is associated with increased levels of pro-inflammatory cytokines (14), and reduced levels of anti-inflammatory cytokines (15).  In addition, vitamin D might help to increase regulatory T cells (16) (17), and reduce Th17 cells (18) (19).

Alpha lipoic acid.  Numerous studies show that alpha lipoic acid can reduce pro-inflammatory cytokines such as TNF-alpha, while downregulating NFkB (20) (21) (22).  There is also evidence that alpha lipoic acid can suppress the number of Th17 cells, while increasing the number of regulatory T cells (23).

Probiotics.  Certain strains of probiotics can help to reduce inflammation by reducing pro-inflammatory cytokines and modulating NFkB (24).  Some probiotics, including Lactobacillus reuteri and Lactobacillus casei, have been shown to increase regulatory T cells (25).

Green Tea.  Studies show that the green tea polyphenols can help to downregulate NFkB and increase regulatory T cells (26) (27) (28).  In fact, the studies show that even decaffeinated green tea, which has reduced catechin content, doesn’t necessarily reduce its ability to inhibit NFkB (28).

Gamma-linolenic acid.  Although most omega-6 fatty acids are considered to be pro-inflammatory, this isn’t the case with gamma-linolenic acid (GLA).  Studies show that GLA can decrease proinflammatory cytokines (29) (30).  Some excellent sources of GLA include borage oil, evening primrose oil, and black currant seed oil.

You might have noticed that in addition to reducing pro-inflammatory cytokines, many of the nutrients/herbs I mentioned in this post increase regulatory T cells and decrease Th17 cells.  I’ve spoken about these in past articles and blog posts, as regulatory T cells help to suppress the autoimmune response, while Th17 cells promote autoimmunity.  The good news is that some of the same nutrients and herbs which reduce proinflammatory cytokines will also increase regulatory T cells and decrease Th17 cells:

In summary, while some healthcare professionals recommend for their patients to get tested for cytokines to determine if they are Th1 or Th2 dominant, this has certain limitations.  Although autoimmunity involves an imbalance of the Th1 and Th2 pathways, it is difficult to balance these pathways by using specific nutrients and herbs.  And in my opinion, this is the only reason to test for cytokines in the first place.  I personally don’t have my patients test for cytokines.  With regards to reducing pro-inflammatory cytokines (and increasing Tregs and decreasing Th17 cells), natural agents which seem to benefit many people with both Graves’ Disease and Hashimoto’s Thyroiditis include turmeric, resveratrol, vitamin D3, alpha lipoic acid, probiotics, and green tea.