Understanding the Th1 System
Th1/Th2 Theory 101
You’ve probably heard quite a bit 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 .
According to the Th1/Th2 theory :
- 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
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 .
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 .
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 .
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].
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 .
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 .
On the other hand, male sex hormones or androgens may increase PPAR alpha, which causes inhibition of Th1 dominance in animals. At the same time, men tend to have lower PPAR gamma, which is hypothesized to lead to Th17 dominance .
To some extent, researchers believe that Th1 and Th17 “compete” with each other, but this is also uncertain. Some studies indicate that IL-2 produced by Th1 cells activates STAT5, which competes with STAT3 (thought to be produced in Th17 dominance) .
More human research on gender-related mechanisms is needed.
If your goal is to lower your Th1 response because you have serious immune problems – including autoimmunity, and constant fatigue or pain – it’s important to talk to your doctor, especially your symptoms are significantly impacting your daily life.
Your doctor should diagnose and treat any underlying conditions causing your symptoms.
Remember that the existing evidence does not suggest that Th1 dominance causes autoimmunity. Complex autoimmune disorders always involve multiple possible factors – including biochemistry, environment, health status, and genetics – that may vary from one person to another.
Therefore, you may try the strategies listed below if you and your doctor determine that they could be appropriate. Read through the approaches we bring up and discuss them with your doctor before trying them out. This is particularly important if you plan to take any dietary supplements.
Most of the lifestyle, dietary, and supplement factors listed below rely on animal and cellular data. These findings can’t be applied to humans. Clinical research is needed before the safety and effectiveness of any approach listed below is determined.
Thus, we’re providing a summary of the existing research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
Supplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.
Additionally, supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. That’s why it’s so important to consult your healthcare provider before supplementing and let them know about all drugs and supplements you are using or considering.
People who think they are Th1 dominant may have an underlying, active infection. Inhibiting the Th1 system should be avoided as it may lower immunity and worsen the infection.
People with weakened immune systems, such as HIV patients, people on immune-suppressing medications, and the elderly should avoid approaches that lower Th1 activity.
Dosage may also matter and different doses will have different effects on Th1/Th2 balance. Safe supplement doses should not be exceeded.
Finally, have in mind that none of these strategies should ever be done in place of what your doctor recommends or prescribes.
- Fasting  (Decrease IFN, increases IL-4)
- Sun/UVB light . UVB may decrease IFNy in Th1 dominance but increase it in Th2 dominance, decrease IgE responses and IL-12 [8, 9, 10].
- Circadian Rhythm entrainment. Th1 responses are suggested to be lowest at 6 am, in sync with cortisol peak [11, 12].
- Acupuncture 
- Classical conditioning , Overtraining 
The following detrimental factors may also raise Th1 and should be avoided: severe injury , Mycotoxins, Mold , Diesel exhaust particles , Glutathione depletion , Oxidative stress/ROS [20, 21].
- Fish 
- Egg white/ovalbumin 
- Soy 
- Avocado 
- Rice 
- Watermelon 
- Apple polyphenols 
- Papain/Papaya 
- Bromelain/Pineapple 
- Extra virgin olive oil/Omega 6 PUFAs, Black Cumin Seed Oil 
- Hemp oil and evening primrose oil 
- Blueberry  (IL-12, IFNy)
- Sesame oil (IFNy) without increasing Th2
- Cinnamon/NaB [33, 34], (IL-12, IFNy)
- Carob/ D-pinitol  (IFNy, IL-12)
- Cardamom 
- Fennel 
- Mustard 
- Pistachio nuts 
- Cantaloupe 
- Vitamin A sufficiency  (potentially higher than RDA levels, though more research is needed). Proposed to reduce IFN-γ, T-bet, and IL-12R [42, 43].
- Omega-3’s and Fish oil 
- Calcium 
- Chromium [45, 46, 47] (proposed to decrease TNF-alpha) 
- Manganese 
- Lecithin/Choline sufficiency . These nutrients are found in eggs and meat.
- Fish oil 
- CBD (be sure to check if CBD is legal in your state or country) [50, 51, 52]
- Curcumin (in the morning) 
- Olive leaf extract [54, 55], (IFNy)
- Andrographis [56, 57] (IFNy, IL-2)
- Resveratrol 
- Pregnenolone (58)
- EGCG  (may not increase Th2)
- Boswellia  (via IL-12, IFNy) 
- Theaflavins [61, 62] (found in black tea) (potently suppresses IL-2, IL-12, IFNy, IL-4, IL-5)
- Fisetin  (in strawberries) (IL-12)
- Black Cumin Seed Oil 
- Bile 
- Icariin 
- Probiotics… L. lactis  , B. fragilis , L. Plantarum , B. infantis , B. Bifidum , B. Breve , L. Helvetica , S. Boulardii  (contradictory), B. Subtilis  (typically found in common Probiotics)
- Inosine/Uric Acid 
- Molecular hydrogen 
- Silymarin /Silibinin, (IL-12)
- Ursolic acid , (IL-2, IFNy)
- Hydroxytyrosol  (IL-12)
- Emodin (found in rhubarb) 
- Theanine  (IFNy)
- Honokiol 
- Berberine 
- Forskolin 
- Glucosamine , (IFNy)
- Ginkgo  (IFNy)
- American Ginseng [87, 88] (IFNy)
- Nettle leaf  (IL-2, IFNy)
- Parthenolide  (IFNy)
- R-Lipoic Acid 
- Artemisinin  – Contradictory 
- Astaxanthin 
- Danshen  (maybe only inhibits IL-1b) 
- Cat’s claw 
- St John’s Wort/Hyperforin 
- Hops (xanthohumol)  (IL-2, IFNy)
- Synephrine 
- Caffeine (Chronic) 
- Aloe  (IFNy)
- Plumbagin (black walnut hull) 
- Bilberry /Anthocyanins 
- Vitamin D3 
- Melatonin  (IFNy)
- Apigenin [107, 108] (IFNy, IL-12)
- Luteolin [108, 109, 110] (IFNy)
- Myricetin (in veggies) [111+112] (IL-12)
- Citrus Bioflavonoids: Naringin  (in grapefruit)  (via IFNy)
- Rutin  (IFNy)
- Chrysin 
- Baicalin [117, 118] (IFNy, IL-12)
- Chlorogenic acid  (in coffee, plants)… Contradictory – increased IL-12 
- Rosmarinic acid  (in oregano and sage) (IFNy, IL-2)
- Oleanolic acid  and triterpenes  (found in olive products, garlic, medicinal plants)
Have the following limitations in mind first:
- Corticosteroids, hormones, and other medications should only be used with a doctor’s prescription.
- Pregnenolone is an unapproved drug with a high potential for harm.
- Brain chemistry is not something that people can change on their own with the approaches listed blog posts.
Additionally, the following hormonal factors and neurotransmitters are theoretical. They aren’t backed up by solid science. We bring them up for informational purposes.
- Pregnenolone 
- Progesterone . Increases IL-10. Increases immune tolerance so that fetus isn’t rejected. Pregnancy improves the symptoms of rheumatoid arthritis, a disease driven primarily by Th1 immune responses, whereas systemic lupus erythematosus, a disease linked to excess Th2 cytokine production, tends to flare during pregnancy .
- Testosterone [125, 126]. Hypothesized to decrease IL-12 and increase IL-10, which decreases TNF and IL-b.
- Estrogens/Estradiol [127, 128]. Plant-based foods have phytoestrogens, especially soy, but their effects on Th1 immunity haven’t been researched.
- Insulin 
- ACTH 
- MSH 
- TRH 
- Somatostatin 
- Norepinephrine (131, 132)
- Serotonin  Inhibits TNF, IL-12 and increases IL-10, NO, and PGE2.
- Dopamine 
- Histamine 
- GABA (A) 
- Steroidal anti-inflammatories such as glucocorticoids (Dexamethasone) or cortisol  i.e.
- Low Dose Naltrexone (LDN)? [138, 139] (conflicting); LDN is a controversial approach.
- Ketamine (drug) 
- Valproic acid  (Drug)
- Metformin  (Drug)
- Methotrexate (Drug) 
Scientists are investigating whether the following pathways reduce Th1 patterns in animals and cells:
- Inhibiting mTOR is a significant pathway to decrease Th1 Cells.
- Inhibiting NF-kB
- Inhibiting STAT3 
- Galectin-1 
- Inhibiting Ace 
- Inhibiting Proteasome (-) 
- STAT1 inhibition 
- GSK3 inhibition , HDAC (-) 
- PDE4 inhibition 
- PPAR delta activation 
- DPP-4 inhibition 
- IL-10 activation 
- MCP-1 
- Spermine 
Human data are lacking.
It’s always a good idea to avoid unhealthy habits – such as smoking, fast food, overeating, being under a lot of stress, and drinking too much – that can bring your immune system out of balance. Look to get regular exercise, enough nutrients, sleep, and follow a healthy circadian rhythm.
- How to decrease Th2 dominance
- How to decrease Th17 dominance
- How to decrease dominance in both Th1 and Th2
- How to decrease TNF
- How to decrease IL-1
- How to decrease Nf-kB
- How to decrease IL-6
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Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
Joe personally follows the lectin avoidance diet and claims it helped him lower Th1 dominance. He says that lectins exacerbate his Th2-related inflammation and sticks with low lectin foods. This approach is based on his personal experience only.
Some people prefer taking Th1- increasing supplements at night rather than in the day. Scientists are researching whether Th1 cells produce cytokines such as TNF-alpha  and IL-1beta  – implicated in fatigue – at night, but this hasn’t been proven. They also claim that many herbs that increase Th1 also decrease IL-1beta and TNF-alpha, pointing out that it isn’t so simple.
If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation wellness report by our sister company, SelfDecode. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.