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Are You Th1 or Th2 Dominant? Effects + Immune Response

Written by Puya Yazdi, MD | Last updated:
Medically reviewed by
Genius Labs Science Team | Written by Puya Yazdi, MD | Last updated:

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Immune balance may help guide what people eat or avoid, the supplements they take, and the types of exercise they prefer. However, science only backs up some immune-centered approaches. When does the Th1/Th2 theory hold and what does it mean for health? Read on to learn more about Th1 and Th2 dominance.

Are You Th1 or Th2 Dominant?

Understanding the Basics

You’ve probably heard something about the Th1 and Th2 response if you’ve reached this article.

Let’s get some basics down first.

To start with, the human immune system is incredibly complex. We have many types of immune cells that are orchestrated by various factors–from our encounter with microbes, to our health status, genetics, mood, and more.

The Th1/Th2 theory is one attempt at understanding immune regulation, and Th1 and Th2 cells are its key players. This theory dates back to studies on mouse immune cells in the 80s. However, it is still considered controversial and it’s not without limitations and discrepancies. More large-scale human studies are needed to determine its validity [1].

According to the Th1/Th2 theory [1]:

  • Th1 cells drive the so-called type-1 pathway (“cellular immunity”). They are thought to be involved in fighting viruses and other pathogens that enter cells, getting rid of cancerous cells, and triggering delayed-type hypersensitivity (DTH) skin reactions.
  • Th2 cells drive the type-2 pathway (“humoral immunity”). They are hypothesized to increase antibody production and fight invaders that are outside cells. They may be involved in tolerance of organ transplants (xenografts) and of the fetus during pregnancy

 

Anecdotal Claims

Some people claim that whether a person is Th1– or Th2-dominance makes a big difference. According to some, it might affect supplement, lifestyle, and diet recommendations.

Unfortunately, though, we are lacking proper clinical trials to verify this stance. That means there’s just not enough evidence to tailor supplements, lifestyle choices, and diet to a person’s immune profile.

Additionally, people can’t tell if they are Th1- or Th2-dominant based on symptoms or reactions to supplements.

Thus, if you think that you have an immune imbalance–possibly related to Th1 or Th2 overactivity–it’s important to see your healthcare provider. He or she will ensure you get an accurate diagnosis and adequate treatment.

Lastly, there are several gaps in the Th1/Th2 theory. Scientists often speak about its inconsistencies and limitations. This doesn’t mean it’s false but that it doesn’t always hold.

Inconsistencies & Limitations

The Th1/Th2 theory states that overactivation of either the Th1 or the Th2 pattern can cause disease. Similarly, either pathway is thought to down-regulate the other [1].

One of the reasons why an increase in one may translate to a decrease of the other is because they differentiate from a progenitor or original cell and there’s a limited number of these cells.

Based on this, some studies claim that most substances that decrease Th1 will increase Th2 and vice versa (decrease Th1 will increase Th2), but this isn’t always the case.

Some nutrients–including long-chain omega-3 fatty acids (EPA and DHA)–seem to improve various inflammatory and autoimmune conditions without any specific Th1/Th2 effect [1].

Often, it’s uncertain whether a certain nutrient or intervention stimulates the Th1/Th2 immune system or not.

Additionally, many diseases that were previously classified as Th1- or Th2-dominant failed to meet defined criteria. Plus, Th1 dominance can be polarized to Th2 patterns, and vice versa [1].

The main issue with the whole Th1/Th2 theory, as some scientists have recently pointed out, is that the activity of cytokines and other immune messengers rarely fall into strict Th1 or Th2 patterns. Some cells, like non-helper regulatory T cells (Tregs), may influence both Th1 and Th2 responses [1, 2, 3].

New Research

So-called Th17 cells were identified only recently and scientists think they can fill the missing gaps and explain some inconsistencies with the Th1/Th2 theory [4].

Th cells are short for T helper cells. Scientists say that T helper cells are kind of like a symphony conductor. The conductor sends signals to the band and the musicians play the music. T helper cells send signals–or, more technically, release cytokines–that guide other immune cells that do the attacking.

In turned out that about a third of the progenitors – T helper cells – develop into Th17 cells, a third into Th1, and a third into Th2 cells [4].

A naive T cell can either become an inflammatory Th17 cell or an anti-inflammatory Treg cell. According to some researchers, the goal in inflammation is to convert more Th17 cells to Treg cells [4].

However, Th17 science is new and the findings so far have been inconclusive.

With all this in mind, let’s now take a look at how much we know about Th1 and Th2 immune patterns.

Th1 Dominance

Overview

Th1 cells are part of what’s called cell-mediated immunity, which is an immune response that does not involve antibodies but does involve the release of various cytokines in response to foreign proteins [1].

Th1 dominance has been linked with delayed-type hypersensitivity [1].

It’s thought to be caused by the overstimulation of immune cells, commonly lymphocytes (Natural killer cells, T cells) and macrophages, potentially resulting in chronic inflammation [1].

Interferon-gamma (IFNy) is considered to be the main cytokine in Th1 dominance. It inhibits the production of most IgG and IgE antibodies and increases the secretion of IgM [5, 6].

Does Food Affect it?

Limited studies suggest that food processing may also matter, since cooking may alter proteins/antigens. For example, there are less IgM antibodies to raw peanuts than cooked peanuts [7].

There are also more IgM antibodies to fried chicken, canned tuna and fried salmon [7].

Anecdotally, some people claim they get more inflammation from canned tuna than from fresh tuna. But many other factors may come into play and no scientific studies attest to this effect.

It’s also uncertain how cooking various foods affects the immune response.

Associations

The majority of studies covered in this section deal with associations only, which means that a cause-and-effect relationship hasn’t been established. The same goes for the associations listed under the Th2 dominance section.

For example, just because fatigue has been linked with Th2 overactivity doesn’t mean that fatigue is caused by Th1 dominance. Data are lacking to make such claims.

Also, even if a study did find that Th1 dominance contributes to fatigue, it’s highly unlikely to be the only cause. Complex health issues like chronic fatigue, autoimmune disorders, and others always involve multiple possible factors–including body and brain chemistry, environment, health status, and genetics–that may vary from one person to another.

The following have been associated with Th1 dominance in limited studies:

  • Delayed food sensitivities: This might be evidenced by getting inflammation from food, yet the effects aren’t necessarily immediate [8].
  • Fatigue: After meals and acute exercise or fatigue, in general, have been described as more severe in Th1 dominance. Scientists think Th1 cells increase the cytokine interferon-gamma, which increases other cytokines like IL-1b and TNF-alpha. These may cause fatigue via suppression of orexin neurons. TNF-alpha may also be elevated in Th2 dominance because it can be released by IL-1 and mast cells, but it’s likely more elevated in Th1 dominance. Proper human data for this link are lacking [9, 10, 9].
  • IBS: A couple of small studies suggested that people with IBS may be more likely to be Th1 dominant (elevated IL-12), though findings have been inconclusive. Interferon is hypothesized to reduce serotonin in the gut and increase oxidative stress (by activating IDO). However, there are many inconsistencies and people with Th2 overactivity can also have IBS [11, 12].
  • Rheumatoid arthritis [13]
  • Hashimoto’s thyroiditis (IL-18) [14, 15]
  • Low T3/Euthyroid sick syndrome: When levels of T3 and/or T4 are low but the thyroid gland does not appear to be dysfunctional. This syndrome has been linked with higher IL-6, Interferon gamma, TNF-alpha, and IL-1b. However, there’s not enough evidence to draw any conclusions [16. 17. 18. 19].
  • Potentially more thin: According to some clinical observations that remain unproven, the majority of Th1 dominant people tend to be relatively thin. Some researchers think this might be explained by 2 mechanisms:
    • 1) TNF-alpha and IL-1beta inhibit orexin, which may decrease appetite. TNF-alpha also seems to lead to increased fat-burning in animals and insulin resistance in fat cells. Small studies found that anti-TNF-alpha therapy may result in weight gain – an average of 5.5 kg or 11 pounds in only 12 weeks. Larger human studies are needed [20, 21].
    • 2) Interferon-gamma, like TNF-alpha, is hypothesized to create insulin resistance in fat cells and differentiation of fat cells, which may prevent fat storing. There are many other aspects to hunger and weight gain that this theory doesn’t take into account, though [22, 23].
  • IBD: may be characterized by a different cellular subset: Th17 cells and IL-18, a pattern loosely connected with Th1 dominance [24, 25].
  • Psoriasis and rosacea [26, 27]
  • Celiac disease [28]
  • Crohn’s disease [29]
  • Type 1 diabetes [30]
  • PCOS (IL-18) [31]
  • Alzheimer’s (IL-18) [32, 33]
  • Lupus (also Th2) [34]
  • Multiple sclerosis (also Th2) [35]
  • Guillain-Barré syndrome [36]
  • Post-infectious IBS [37]
  • Behcet’s [38]
  • Vitiligo (Th1 chemokine) [39]
  • Inflammation after the following: Strep, mono (EBV), HPV, herpes, pneumonia, H. pylori or Cytomegalovirus. These are common infections that also invoke the Th1 system; in some people, the immune system remains active after these infections. In some environments, this may have been a survival advantage that made people more likely to survive into adulthood and bear offspring [40, 41, 42, 43, 44, 45].
  • Chemotherapy-induced neuropathy has increased CCL2 and IFNy, and lower levels of IL-10 [46, 47].

More human data are needed. Most of these associations remain insufficiency proven.

Learn about factors that may balance an elevated Th1 system in this post.

Checking for Imbalances

Trouble with inflammation and food intolerances without classical Th2-dominant symptoms have been anecdotally associated with Th1-dominance.

If you’re experiencing these symptoms, be sure to see a doctor to uncover the underlying cause and get an accurate diagnosis.

Immune defense–and Th1 dominance as one part of it–is shaped by a combination of genetics and environment. One of the factors in our environment that can affect immunity are infections.

Bacterial and most viral infections activate the Th1 system. But it’s not as simple. More frequently, both Th1 and Th2 responses are required at different time points to get completely rid of the foreign invader–although Th1 may be more important [48, 49].

Th1 responses are suggested to be lowest at 6 am, in sync with cortisol peak [50, 51].

Some scientists hypothesize that interferon gamma is the major cytokine involved with Th1 dominant people [52].

According to one theory, chronic, low-grade interferon gamma (“Th-1 type inflammation”) might accelerate aging and aging-related health problems, based on lab animal research. Animal findings can’t be applied to humans, though [52].

Nonetheless, interferon gamma is proposed to be a potential contributor to age-related psychiatric conditions (such as depression, anxiety, insomnia, and cognitive impairment) and medical diseases (such as cardiovascular diseases, neurodegeneration, osteoarthritis and osteoporosis, and diabetes). Solid data are lacking to back this up [52].

Are there Benefits to an Elevated Th1 System?

Some researchers think that having an elevated Th1 immune system may have some benefits, though clinical studies have yet to confirm whether this approach is helpful.

One theory states that people with Th1 dominance tend to get sick somewhat less than others because their immune system is on guard. There may be some truth to this. For example, the flu vaccine works in part by boosting Th1 activity [53].

However, chronic stress will weaken the immune system regardless of Th1/Th2 tendencies [54].

Scientists are also investigating whether the Th1-pathway can protect against cancer, though research is still in the early stages. The following mechanisms are an area of research [55]:

If Th1 cells and cytokines like interferon gamma and TNF scour the body for tumor cells and destroy them. Some have suggested that there is a trade-off with cancer and autoimmunity, but newer research suggests it’s not nearly as simple. Some cancers like multiple myelomas are considered to be Th1 dominant [56].

The unproven generalization goes that the more active a person’s immune system is, the more likely their body will destroy cancer cells before they start multiplying out of control. According to this view, a more active immune system is also more likely to mistake the body’s own tissue as a foreign invader and attack it.

Still, experts agree that immune balance is important. Speak with your doctor about any immune imbalances you may have and follow their recommendations. Supplements and dietary changes can be a complementary approach.

Th2 Dominance

Overview

Th2 cells are said to mediate the activation and maintenance of the “humoral” or antibody-mediated, immune response.

Popularly, Th2 dominance is considered an “anti-inflammatory profile” because people with this profile are claimed to have lower levels of systemic inflammation. The negative effects of Th2 dominance are also said to be more benign than Th1 dominance. There’s no proper data to back up these claims, though.

For example, some researchers regard allergy as a Th2-weighted imbalance–and allergic reactions are known to be inflammatory [49].

People with Th2 dominance may produce more antibodies and instant food allergies might be more likely to occur, according to limited data [49, 1].

People with Th2 dominance, in general, do not necessarily have a “weaker immune system.” However, they may be better at fighting infections that take hold outside of cells (extracellular infections)–though the evidence is inconclusive [1].

The Th1/Th2 theory states that the dominant cytokine in Th2 dominance is IL-4, which produces IgG1 and IgE but markedly inhibits IgM, IgG3, IgG2a, and IgG2b [5].

Th2 cells are produced by IL-2 and IL-4 and they give off IL-4, IL-5, IL-6, IL-10, and IL-13 (see picture above).

Does Food Affect it?

It’s still unknown how various food items might influence Th2 activity.

One study found food processing has an effect on IgE levels. Raw eggs, raw peanuts, and raw pecans didn’t raise IgE antibodies as much as cooked eggs. The authors suggested that Th2 dominant people might do better with raw eggs, raw peanuts, and raw pecans, at least in one respect. However, these findings need to be replicated in larger trials [7].

Associations

Remember that these studies deal with associations only, which means that a cause-and-effect relationship hasn’t been established.

Even if a study did find that Th2 dominance contributes to allergies, it’s highly unlikely to be the only cause. Complex health issues like allergies always involve multiple possible factors–including body and brain chemistry, environment, health status, and genetics–that may vary from one person to another.

The following have been associated with Th2 dominance in limited studies [1]:

  • IgE-related allergies, which are immediate and can be measured by skin scratch tests [57]
  • Seasonal allergies
  • Airway constriction
  • Asthma
  • Nasal drip
  • Mucus
  • Eczema (Dermatitis)
  • Hay fever (Allergic rhinitis)
  • Increased stomach acidity or GERD
  • Excess histamine or what some people call “histamine intolerance”
  • Hives (Urticaria)
  • Chronic Fatigue Syndrome [58]
  • Autism [59]
  • Uveitis, Grave’s disease, Sjogren’s, Oral Lichen Planus, SLE (also Th1 dominant) [60, 61, 62, 63]

Learn about factors that may help rebalance an elevated Th2 system here.

Types 1, 2, and 3 hypersensitivities are thought to be caused by Th2 dominance, though some findings have been mixed [64].

Some effects are hypothesized to stem from the main Th2 cytokine, IL-4, and IgE antibodies. These are claimed to stimulate mast cells to release histamine, serotonin, and leukotriene to cause airway constriction and intestinal peristalsis. However, these pathways have only been investigated in animals. Human data are sparse [1].

According to limited studies, Th2 dominance has also been linked with parasite or helminth infections. Parasites are not the only trigger of the Th2 response, though [1].

Scientists are also investigating whether acute bouts of Th2 immunity can protect against cancer, while chronic elevations have been linked with breast cancer, colorectal cancer, and pancreatic cancer. The link between Th2 and cancer is highly uncertain, though, and it remains unproven [65].

Remember, it’s fully possible to have both Th1 and Th2 elevations [1].

Are There Benefits to it?

The Th2 immune system is considered to be an anti-inflammatory profile, but evidence goes against this claim. Many allergic diseases that have been linked with Th2 activity are inflammatory, while several autoimmune diseases show mixed Th1/Th2 patterns [1].

Some say that a major shift to the Th2 system can be problematic precisely because of allergies.

Additionally, studies indicate that pregnancy is a Th2 state. Scientists think that lower Th1 activity is part of the adaptive physiological response that women go through in pregnancy [1].

This is said to prevent the mother’s antibodies from mounting an attack against the fetus. It’s also thought to explain why women are more prone to infections during pregnancy. Many women with rheumatoid arthritis – typically seen as a Th1 disease – experience relapses after pregnancy [1].

It may also seem odd why Th2 dominant people have increased stomach acidity. According to one unverified theory, gastric fluid acidification may be a way for the body to expel parasite–a response that may have served an important purpose in our evolutionary history [1].

Since parasites activate Th2 immunity, this is possible. However, it hasn’t been proven in proper human studies [49].

Th1/Th2 Dominance and Methylation

Some researchers have proposed that a Th1-dominant state lowers methylation of certain genes. This hasn’t been proven [66, 67, 68, 69, 70].

Poor methylation may have a ripple effect throughout the immune system [71].

In both Th1 and Th2 dominance, some genes are suspected to be over-methylated and some under-methylated. The exact genetic pathways that are affected and their health implications are still unknown.

Even so, some people take TMG, SAM-e, and B-vitamins to support methylation and immune balance. Evidence is currently lacking to back them up.

Conditions Without Th1/Th2 Dominance

As mentioned, the immune system contains more than just Th1 and Th2 cells and their cytokines. Many conditions haven’t been linked with either Th1 or Th2 dominance.

The list below is not a definite one. More conditions might be neither Th1 nor Th2 dominant.

Diseases List

  • Autism [72]
  • IBS and ADHD are associated with inflammation, but can have elevations of either Th1 or Th2 systems [73, 74]
  • Heart disease is from IFN-gamma, VEGF, TGF-beta1. IL-10 has protective effects [75, 76]
  • Schizophrenia, as some studies show it’s Th1 dominant, while others show elevated TNF-alpha and IL-6 is the culprit [77, 78]
  • OCD cytokine profiles vary, but meta-analyses only showed a reduction in IL-1b in people with OCD as a common denominator [79]
  • Ulcerative colitis has no dominant system, but has increased IL-8 levels [80]
  • Carpal tunnel syndrome has increased IL-2, a Th1 cytokine [81]
  • Diabetic neuropathy has elevated IL-18 and TGF-beta – there’s no dominant profile here. Other inflammatory factors include PDGF AA/BB, RANTES, leptin, osteoprotegerin, G-CSF, sE-Selectin, sICAM, sVCAM, CRP and fibrinogen. Patients with painful neuropathy had higher sICAM-1 and CRP levels when compared to painless neuropathy [82, 83, 84]

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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