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Cytokines, Mast Cells, and Mast Cell Activation Syndrome: What to know if you have Mast Cell Activation Syndrome or Histamine Intolerance

If you have Mast Cell Activation Syndrome or Histamine Intolerance (or both!), you may have heard of cytokines.

But maybe you weren’t really sure what cytokines were. Then last year, cytokines became a household word because of current events.

So what are cytokines? Where do they come from?

How are they involved with mast cell issues?

So, let’s jump right in!

We’ll start by talking about what cytokines are.

But first, a quick reminder:

This article is for informational educational purposes only. It’s not meant to treat, diagnose, or prevent illness. So please, always work with your healthcare provider.

What Are Cytokines? – What to Know for People with Mast Cell Activation Syndrome and Histamine Intolerance

Cytokines are signalers. That’s the big thing to know about them.

They are a type of protein that communicates to several types of immune system cells.

Basically, when cytokines are released, they signal the immune system to do its job. One example would be if a bacterial or viral invader is present. The immune system needs to take them out.

This is a microscopic picture of a cytokine:


The body has many types of cells which produce cytokines. They are all immune related cells. Today, we’ll focus on one of the most important types in your body: Mast Cells.

Here’s a brief overview about your mast cells:

Mast cells can be triggered by all kinds of things. That’s where we get mast cell activation.

Mast Cells can be triggered by viruses or bacteria. They can also be triggered by allergens like pollen. Or even food proteins.

Or they can be triggered by normal things that happen in the body. Things like hormones or neurotransmitters. Or even injuries.

These are just a few things that can trigger a response from mast cells.

And what happens when mast cells get triggered?

They release mediators.

There are all kinds of different types of chemical mediators in mast cells. You might already be familiar with one type: histamine.

But there are actually HUNDREDS of mast cell mediators!

Another very important category of mast cell mediators is the cytokine mediators.

Several cytokines are inflammatory. There are also anti-inflammatory cytokines. But we’ll be focusing on the pro-inflammatory ones related to Mast Cell Activation Syndrome.

Before we go any further, though, let’s briefly review.

When your mast cells have been triggered, they release chemical mediators.

Several of those mediators may be different types of cytokines.

Some cytokines are inflammatory.

And you probably know by now that with Mast Cell Activation Syndrome comes a lot of inflammation.

These are some of the key cytokines which create inflammation:

  • Interleukin-6 (IL-6)
  • Interleukin-1b (IL-1b)
  • Tumor Necrosis Factor alpha (TNFα)

IL-6 and TNFα are key drivers behind something you may have heard about: C-reactive protein. C-reactive protein (CRP) is a measure of inflammation in the body.

And IL-6 is the main player in severe cytokine issues some people get from viral infections.

IL-6 is produced by mast cells and other immune cells. It’s involved in lung issues, sepsis (serious blood infection), and damage to tissues.

And IL-6 and TNFα are usually higher with mold toxicity.

A study was published in the 2005 issue of Clinical and Experimental Allergy. The study found that two mycotoxins (citrinin and gliotoxin) were linked to higher levels of IL-6 and TNFα in the body.

So, you can imagine how mold toxicity can create such serious inflammatory issues.

mold toxins growing

And Mold Toxicity is the #1 Root Trigger I see for Mast Cell Activation Syndrome in my practice.

If you happen to know you have higher levels of IL-6 and TNFα, it’s worth checking for mold toxicity.

So, cytokines can lead to inflammation. That’s one way they can cause issues.

Cytokines can also get out of control. When this happens, it can be very serious.

Serious cytokine issues can happen when the body’s response to an infection becomes over-activated.

Specifically, this can sometimes occur in some people with specific viral infections and conditions like:

  • Flu (like the H5N1 “bird” flu)

  • SARS viruses

  • MERS viruses

  • Multiple Sclerosis

Basically, the inflammation gets out of control. Way out of control.

And when mast cells get over-active, they release more cytokines. And that means more inflammation.

There are certain symptoms to watch for with excess cytokines that can happen with those types of viruses:

  • High fever and chills
  • Swelling of arms, legs, hands, feet
  • Coughing
  • Shortness of breath
  • Muscle and joint pain
  • Severe fatigue
  • Very low blood pressure
  • Clotting issues

Of course, those can be symptoms of other conditions as well. But they are some things to watch for.

Now, I want to be sure we cover what’s called Th1/Th2 balance.

You’ll see its importance as we’re talking cytokines. I’ll break it down into simple terms for you next.

Th1 vs. Th2 Cytokines – What to Know for People with Mast Cell Activation Syndrome and Histamine Intolerance

When we talk about cytokines, we have to talk about the Th1/Th2 balance.

TH1 and TH2 Balanced

Th1 and Th2 are types of cytokines. They are immune cells.

The “Th” stands for “T helper” cells.

Th1 cells make up the initial wave of immune response which kills off viruses and bacteria.

Th2 cells are involved in chronic inflammation.

Your Th2 immune cells kick in when you struggle to get rid of infections. And they cause significant widespread inflammation in your body.

This can happen when your body is struggling with other issues alongside the infection you are trying to fight off. Issues like mold toxins, chemical toxins, and/or a lot of stress.

So, when we have things like mold toxicity, the seesaw gets tipped. When this happens, our T helper immunity looks like this:

TH1 and TH2 Imbalances from mycotoxins

When your Th2 cells become overactive, your Th1 cells become suppressed.

That can lead to all kinds of bacterial and viral Infections. It can even lead to chronic infections like Epstein-Barr. Or the body may not be able to get rid of Lyme and other co-infections.

Related Article: Non Toxic Tick Prevention for those with Sensitivities

And on top of that, you can get an elevated mast cell response.

It kind of creates this loop where the Th1 response is kept down. At the same time, the Th2 response is being kept up. That means the Th2 cytokine is causing more inflammation.

We always have to ask, “Why is this happening? What’s the big thing that’s causing this to happen?” Quite often, it’s mold toxicity.

I’ll come back to it again and again and again. Mold Toxicity is one of our biggest root triggers.

Mold toxins cause a major double whammy in Mast Cell Activation Syndrome. First: they disrupt the Th1/Th2 balance.

Second: mold toxins mess up the nervous system signaling. And that causes even more Mast Cell Activation issues.

(I know, I talk about mold toxins a lot. But it’s because they are a BIG deal in Mast Cell Activation Syndrome. And not enough people are giving it the attention it deserves, yet.)

Chronic stress and a history of early traumas can also affect this Th1/Th2 balance.

The nervous system and immune system are intertwined – you can’t really separate them.

Chronic stress causes major imbalances in Th1/Th2 balance - making it harder to fight off colds, flu, and other viruses. And causing a lot of Mast Cell Activation.

Very targeted nervous system support is one of the most important ways to help get Mast Cells back in balance.

Next, we’ll look at a couple of supplements that could help, too.

Cytokine Balancing Supplements – What to Know for People with Mast Cell Activation Syndrome and Histamine Intolerance

This article is for informational educational purposes only. It’s not meant to treat, diagnose, or prevent illness and the supplements listed below are not prescriptive for any person.

As with all supplements, please start slowly. Most sensitive people do better starting new supplements with a tiny sprinkle. Always talk to your healthcare provider before starting anything new.

So, you saw how much the cytokines play a role in signaling.

We also talked about the Th1/Th2 balance. That’s where the chronic inflammation is high and the pathogen killing is low.

We want to get a better Th1 response and reduce the overactive Th2 response.

Research has shown that certain supplements can be helpful with supporting cytokine balance. Two of my favorite go-tos in the Mast Cell 360 practice are:

  • Perilla seed extract
  • Baicalin (Chinese skullcap extract)

Perilla Seed Extract Actions

Let’s start with a brief overview of the actions of Perilla seed extract. 

Perilla seed extract has been shown to lower histamine. In a study of people with seasonal allergies, perilla helped lessen symptoms.

Plus, Perilla seed extract has been shown in a study to lower TNFα (an inflammatory cytokine). Perilla seed extract has also demonstrated properties as a really good modulator of the Th1/Th2 balance.

Now, let’s look at Baicalin.

Baicalin (Chinese skullcap extract) Actions

Baicalin, again, is an extract from Chinese skullcap. There are several types of Skullcap species. The Baicalin extract can be a little challenging to find.

According to cell studies, baicalin also lowers TNFα (an inflammatory cytokine). Baicalin also suppressed mast cell degranulation and histamine release in animal studies.

I’ve used these a lot for myself and in my practice and have seen great results. So, these two supplements can be a really good place to start for cytokine modulating.

Let’s look at options for these 2 supplements next in detail: 

Perilla Seed Extract

There are 2 sources for Perilla Seed Extract I use the most. I have them linked below. 

You can get them both at Fullscript.

If you want to register an account under Mast Cell 360, you’ll get 15% off any Fullscript supplement order anytime.

I find the Perimine to be a little more effective. But I wanted you to have 2 options in case you have a filler sensitivity:

Baicalin (Chinese Skullcap Extract)

Most skullcap products are actually American Skullcap, which is definitely NOT the same thing. So, be sure to read the label. American Skullcap has very different properties.

The latin name of Chinese Skullcap is Scutellaria baicalensis

I most often use this Chinese Skullcap extract Baicalin.
You can get 10% off Baicalin if you use this coupon code: Mastcell10.

Note: They also carry Baicalein (see the extra e in the name?). It is much more potent, so if you’re sensitive, I’d start with Baicalin.

Super sensitive people may do better starting with a tincture of Chinese Skullcap, though. Here is an option:

Chinese Skullcap (Huang Qin) Tincture (Alcohol Free)

I always recommend if you have Mast Cell Activation Syndrome to start new supplements low and slow with microdosing.

You can learn a lot more about both Perilla Seed Extract and Baicalin, along with possible uses and ways to onboard these in my Top 8 Mast Cell Supporting Supplements Master Class.

I go into a lot of detail in the course on ways to begin new supplements.

You may also have an interest in the class if you would like to learn more about additional mast cell supporting supplements.

Here’s what’s included in this Master Class:

  • The Top 8 Mast Cell Supporting Supplements that your doctor doesn’t even know about
  • In depth on the Actions and Benefits of these 8 Mast Cell Supporting Supplements
  • What supplements NOT to take if you have Mast Cell Activation
  • How to know which these Top 8 supplements can work for you
  • Troubleshooting Supplement Sensitivities
  • How to Introduce Supplements the RIGHT way for Mast Cell Activation
  • The top 7 things to do right away (including supplements and more) during a reaction or a flare-up.
  • What to do if you are still having symptoms.

Ready to work on supporting healthy mast cells and cytokine levels?

Be sure to check out our Top 8 Mast Cell Supporting Supplements Master Class:

If you’re wondering about Oxalates and Salicylates in these 2 supplement options, keep reading…

Oxalates and Salicylates in Perilla Seed Extract and Baicalin – What to Know for People with Mast Cell Activation Syndrome and Histamine Intolerance

Oxalates sharp

I had both Perilla seed extract and Baicalin tested for oxalates. They both tested extremely low oxalate. 

They will have some salicylates. Perilla seed extract is a good bit lower salicylate than Baicalin. I’ve had a number of people with Salicylate Intolerance be able to take Perilla seed extract.

I have some people with salicylate intolerance who can take Baicalin, but not as many.

If you have salicylate intolerance, I also talk about some low-salicylate options in my The Top 8 Mast Cell Supporting Supplements Master Class.

It’s important you know that this blog post is for informational and educational purposes. It’s not meant to treat any health condition or to be prescriptive for anyone. Always be sure to work with your healthcare practitioner.

*Some links in this website are affiliate links, which means Mast Cell 360 may make a very small commission if you purchase through the link. It never costs you any more to purchase through the links, and we try to find the best deals we can. We only recommend products that we love and use personally or use in the Mast Cell 360 practice. Any commissions help support the newsletter, website, and ongoing research so Mast Cell 360 can continue to offer you free tips, recipes, and info. Thank you for your support!

References on What Are Cytokines – What to Know for People with Mast Cell Activation Syndrome and Histamine Intolerance

The American Cancer Society medical and editorial content team. (2019, December 27). Cytokines and Their Side Effects. American Cancer Society. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/cytokines.html.

Bansal, T., Pandey, A., D, D., & Asthana, A. K. (2014). C-Reactive Protein (CRP) and its Association with Periodontal Disease: A Brief Review. Journal of clinical and diagnostic research : JCDR, 8(7), ZE21–ZE24. https://doi.org/10.7860/JCDR/2014/8355.4646

Bui TT, Piao CH, Song CH, Lee C-H, Shin HS, Chai OH. (2017). Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release. Anatomy & Cell Biology, 50(2):124-134. doi:10.5115/acb.2017.50.2.124. 61.

da Silva EZM, Jamur MC, Oliver C. (2014). Mast cell function: a new vision of an old cell. Journal of Histochemistry & Cytochemistry. 62(10), 698-738. doi:10.1369/0022155414545334.

Hsieh C-J, Hall K, Ha T, Li C, Krishnaswamy G, Chi DS. (2007). Baicalein inhibits IL-1β-and TNF-α-induced inflammatory cytokine production from human mast cells via regulation of the NF-κB pathway. Clinical and Molecular Allergy. 5(1)(5):1-10. doi:10.1186/1476-7961-5-5. 63.

Imaoka K, Inoue S, Takahashi T, Ojima Y. (1993). Effect of Perilla frutescens extract on anti-DNP IgE antibody production in mice. Japan Journal of Allergology, 42, 74–80.

Isis M. (1998). The golden root: Clinical applications of Scutellaria baicalensis Georgi flavonoids as modulators of the inflammatory response. Alternative Medicine Review, 3, 472-480. 62.

Johannessen, L. N., Nilsen, A. M., & Løvik, M. (2005). The mycotoxins citrinin and gliotoxin differentially affect production of the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin-6, and the anti-inflammatory cytokine interleukin-10. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 35(6), 782–789. https://doi.org/10.1111/j.1365-2222.2005.02249.x

Kim D-S, Son E-J, Kim M, Heo Y-M, Nam J-B, Ro JY, Woo S-S. (2010). Antiallergic herbal composition from Scutellaria baicalensis and Phyllostachys edulis. Planta Medica, 76(7), 678-682. doi:10.1055/s-0029-1240649. 64.

Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N and Nagai H. (2000). Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clinical and Experimental Allergy, 30, 501-508.

Makino T, Furuta Y, Wakushima H, Fujii H, Saito K and Kano Y. (2004). Antiallergic effect of Perilla frutescens and its active constituents. Phytotherapy Research. 17, 240-243.

Makino T, Furuta Y, Wakushima H, Fujii H, Saito K and Kano Y. (2001). Effect of oral treatment of Perilla frutescens and its constituents on type-I allergy in mice. Biological and Pharmaceutical Bulletin, 24(10), 1206-1209.

Sanbongi C, Takano H, Osakabe N, Sasa N, Natsume M, Yanagisawa R, Inoue K-I, Sadakane K, Icinose T and Yoshikawa T. (2004). Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model. Clinical & Experimental Allergy, 34, 971-977.

Shin, T, Y., Kim, S. H., Kim, S. H., Kim, Y. K., Park, H. J., Chae, B. S., Jung, H. J., Kim, H. M. (2000). Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Perilla frutescens. Immunopharmacol Immunotoxicology, 22(3);489-500.

Shin, T, Y., Kim, S. H., Kim, S. H., Kim, Y. K., Park, H. J., Chae, B. S., Jung, H. J., Kim, H. M. (2000). Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Perilla frutescens. Immunopharmacol Immunotoxicology, 22(3);489-500.

Spoerl, D., Nigolian, H., Czarnetzki, C., & Harr, T. (2017). Reclassifying Anaphylaxis to Neuromuscular Blocking Agents Based on the Presumed Patho-Mechanism: IgE-Mediated, Pharmacological Adverse Reaction or “Innate Hypersensitivity”?. International journal of molecular sciences, 18(6), 1223. https://doi.org/10.3390/ijms18061223

Takano H, Osakabe N, Sanbongi C, Yanagisawa R, Inoue K-I, Yasuda A, Natsume M, Baba S, Ichiishi E-I and Yoshikawa T. (2004). Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. Exp Biol Med, 229, 247-254.

Ueda H, Yamazaki C and Yamazaki M. (2002). Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biological and Pharmaceutical Bulletin, 25(9), 1197-1202.

Wang G, Mohammadtursun N, Lv Y, Zhang H, Sun J, Dong J. (2018). Baicalin Exerts Anti-Airway Inflammation and Anti-Remodelling Effects in Severe Stage Rat Model of Chronic Obstructive Pulmonary Disease. Evidence-Based Complementary and Alternative Medicine. 7591348, 1-14. doi:10.1155/2018/7591348.

Xu L, Li J, Zhang Y, Zhao P, Zhang X. (2017). Regulatory effect of baicalin on the imbalance of Th17/Treg responses in mice with allergic asthma. Journal of Ethnopharmacology, 208, 199-206. doi:10.1016/j.jep.2017.07.013. 60.

Yano S, Tachibana H and Yamada K. (2005). Flavones suppress the expression of the high-affinity IgE receptor Fc‐RI in human basophilic KU812 cells. Journal of Agricultural and Food Chemistry, 53, 1812-1817.

Yano S, Umeda D, Maeda N, Fujimura Y, Yamada K and Tachibana H. (2006). Dietary apigenin suppresses IgE and inflammatory cytokines production in C57BL/6N mice. Journal of Agricultural and Food Chemistry, 54, 5203-5207.

Yano S, Umeda D, Yamashita T, Ninomiya T, Sumida M, Fujimura Y, Yamada K and Tachibana H. (2007). Dietary flavones suppresses IgE and Th2 cytokines in OVA-immunized BALB/c mice. European Journal of Nutrition, 46, 257-263

Yan X, Yan J, Huang K, Pan T, Xu Z, Lu H. (2017). Protective effect of baicalin on the small intestine in rats with food allergy. Life Sciences. 191, 111- 114. doi:10.1016/j.lfs.2017.09.036. 65.


  1. Teersa

    Your picture at the top is a rendering by scientificanimations.com not a microscopic picture of cytokines. Additionally, The blue portion is a cell and the tiny pink dots are the cytokines.

    1. Suz, Mast Cell 360 Team

      Hi Teersa,
      Thank you so much for letting us know it is a rendering!

  2. Brittany Fox

    I recently purchased your supplement
    guide and your master reboot class. How do I sign up for fullscript to get the supplements suggested? I am on a waitlist to hopefully work with you.

    1. Suz, Mast Cell 360 Team

      Hi Brittany,
      To sign up for FullScript, just click on any of the links provided. Type in your email address. If you don’t already have an account associated with that email address, the next step will direct you to set up a password, rather than type one in. If you already have an account associated with that email address, the next step will ask for your password. Once you set up the account through one of our links, you will get 15% off all your orders.
      For HIPAA reasons, could you please contact us via email about any specifics regarding working with Beth? Thank you very much!

      Suz, MC360

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