About Cytokines in Lyme Disease

Lowering inflammatory cytokines made by the immune system is essential for Lyme disease recovery. In this article I discuss why this is so and lay out a nutritional support plan using supplements to lower cytokines. 

Cytokines are proteins made by various types of white blood cells to turn on the immune system to attack invaders like:

• bacteria (for example, Lyme germs and the co-infections),
• intestinal yeast,
• parasites,
• viruses,
• lyme and mold toxins,
• environmental toxins, and
• heavy metals toxins like lead and mercury.

Cytokines are good, right? Well yes and no.

In the right amount they promote healing. In excess, they cause all of the major Lyme disease symptoms and dysregulate the immune system. The problem in chronic Lyme and associated diseases is that they are usually made in excess. Fortunately there are some great steps you can take to lower cytokines.

Good: The right amount of cytokines

• make antibodies work more effectively,
• increase active white blood cells,
• recruit white blood cells to where they are needed,
• turn on white blood cells, and
• decrease viral and bacterial replication.

Bad: Too many cytokines:

• dysregulate the immune system,
• cause pain,
• decrease hormone production from organs like the thyroid and the adrenal glands,
• disturb sleep,
• decrease brain function,
• increase fatigue and tiredness,
• waste muscles,
• cause depression, and
• decrease the function of various organs throughout the body resulting in many other symptoms and medical problems.

Let's Be Clear; They are Excess Cytokine Symptoms

So to be correct, most Lyme symptoms are really excess cytokine symptoms. And other conditions that increase cytokines add to your cytokine pool.

"That is why some people with Lyme disease must also address other cytokine producing problems like MTHFR and mold detox issues, yeast overgrowth in the intestines, parasites, and viral infections."

Herxheimer Die-Off Reactions

A cytokine flare that occurs when a person starts killing Lyme germs is called a Herxheimer die-off reaction. This occurs when the immune system sees dead bug parts from killing Lyme germs and toxins that get released form the inside of the germ. In this situation the immune system makes more cytokines causing a person to feel much worse.

Marty Ross MD Speaks About Cytokines

The recording is from our Lyme Q&A webinar Conversations with Marty Ross MD recorded 3/9/16 when Dr. Ross practiced in Seattle, Washington.

Cytokines: How They are Made and Regulated

Cytokines are made when immune cells are stimulated by germs, toxins, oxidizing agents, other cytokines, other agents, and insomnia.

NF-kB Signals for Cytokine Production

Once the immune cells are stimulated, an intracellular messenger called NF-kB (nuclear factor kappa beta) causes genetic programming for the production of cytokines and the turning on of white blood cells.  Antioxidants like glutathione, quercetin, and curcumin lower oxidation triggers for NF-kB. Supplements, like curcumin also block the function NF-kB.

Kinase Enzymes

Within the white blood cells, the production of cytokines require enzymes called kinases. Herbs that block kinase enzymes, like quercetin, can help lower ctyokines.

Nrf2 Signals Production of Antioxidants.

Cells also have a genetic messenger that increases cell production of antioxidants like glutathione. This messenger is called Nrf2 (nuclear factor 2). There are some supplements like resveratrol and curcumin that turn on Nrf2. Antioxidants decrease oxidizing agents that trigger cytokine production. So turning on Nrf2 creates antioxidants which decrease cytokine production.

Sleep Lowers Cytokine Inflammation in Lyme Disease

Sleep also has a big impact on cytokines. Lack of sleep triggers more cytokines. And high cytokines can cause insomnia. 

How to Lower Cytokines

Get Sleep.

First it is important to get 7-9 hours of sleep a night. Sleep lowers cytokines.

Use Supplements.

To lower cytokines there are a number of interventions to:

• increase antioxidants,
• decrease NF-kB genetic programming of cells,
• increase Nrf2,
• block kinase enzymes and,
• detox.

Antioxidants. Based on the work of Martin Pall, PhD, it is critical to lower oxidizing agents that trigger cytokine production. Glutathione which is made in every cell and its building blocks alpha lipoic acid (ALA) and  n-acetyl cysteine (NAC) are helpful. Curcumin which is a component of turmeric and quercetin are also good antioxidants.

Detox. Glutathione and its precursor building blocks, ALA and NAC also help remove toxins.

NF-kB. Curcumin, quercetin, and resveratrol decrease NF-kB induced genetic signals to produce cytokines.

Nrf2. Curcumin, resveratrol, and black tea extracts containing the polyphenol EGCG increase Nrf2 which increases cell level production of glutathione and other antioxidants.

Kinase Enzymes. Quercetin also blocks kinase enzymes required in the production of cytokines. Blocking kinases with quercetin interferes with the cytokine production line.

Treatment Approach

Step 1: Throughout Treatment

Use a good multivitamin that includes alpha lipoic acid, n-acetyl cysteine, antioxidants, and other micronutrients that decrease oxidizing agents and support liver detoxification. I prefer multivitamin products in powder form made by Thorne or Integrative Therapeutics.

• Sleep 7-9 Hours a Night. See the Sleep Chapter to learn techniques to aid sleep and sleep prescription and supplement options.
• Curcumin 500mg 1-2 pills 3 times a day OR 
• AntiCytokine Combination (Find a combination product that contains curcumin, resveratrol, black tea extract, and NAC. Cytoquel by Researched Nutritionalsis one product that contains these herbs.) 1-2 pills 3 times a day.
• Multivitamin. Use multivitamin powders by Thorne or Integrative Therapeutics. Use as directed on the product label.

Step 2: Add More Anti-oxidants and Detox Agents

For more severe cases add oral glutathione while continuing the multivitamin and curcumin or AntiCytokine Combination. Glutathione is also a great choice if there is nerve pain or numbness. If the addition of glutathione is not effective then consider adding quercetin. This combination works to block the cytokine production line and decreases oxidizing agents that trigger production. These treatments can take 1-2 weeks for maximum effect.

• Glutathione 400-500 mg (as oral liposomal glutathione) 1 or 2 times a day.
• Quercetin 250mg 2 pills 3 times a day.

If glutathione is not tolerated then work with one or a combination of the following anti-oxidants that are used to make glutathione.

• Alpha Lipoic Acid 350 mg 1 pill 2 times a day.
• N-Acetyl Cysteine 500 mg 1 pill 3 times a day.

Step 3: Severe Situations like Herxheimer Die-off Reactions.

For severe situations and bad Herxheimer die-off reactions that are not improving with Step 1 and Step 2 use IV glutathione as a potent antioxidant and to support liver detoxification. This is administered in an integrative medicine physician's office. Another option is to use glutathione in a nebulizer. Glutathione IV is stronger than glutathione by nebulizer in my experience. Using a nebulizer, you breath in a fine mist of the glutathione which is absorbed into the blood throught the blood vessels in the lungs. Sometimes start a person with four IV glutathione treatments and then change to glutathione by nebulizer to continue the treatment.

• Glutathione IV 1200mg to 2500mg 2 times a week for a minimum of four treatments. If it helps but there are still improvements with the last treatment, consider weakly treatments until improvements plateau. You will likely feel more tired after the first treatment.
• Glutathione by nebulizer 200mg/ml 2ml 2 times a day for adults. Children can take 100mg/ml 1ml to 2ml 2 times a day.

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