by Jenny Lelwica Buttaccio
Posted 5/15/20

As COVID-19 continues to dominate news cycles, each day seems to bring about emerging ideas as to the mechanisms that are making some people gravely ill. One dominating theory on what contributes to the intensity and severity of the illness in certain patients: A rapid hyperinflammatory response known as a cytokine storm, suggests a March 2020 article in The Lancet.

Although the topic of cytokines and their impact on the body is likely new for most people, in Lyme disease circles, it’s commonplace to discuss these protein messengers that influence cell-to-cell communications and interaction. That’s because many of the symptoms experienced by people with chronic Lyme disease are due to the prolonged effects of proinflammatory cytokines.

“Cytokines are chemicals that promote inflammation and persistently activate the body’s immune system, leading to a range of problems like fatigue, pain, brain fog, and mood disorders,” says Dr. Bill Rawls, MD, Medical Director of RawlsMD and Vital Plan. Thus, to recover from Lyme disease, it’s critical to lower cytokines and quiet the inflammation that continually kicks up bothersome and debilitating symptoms.

But the immune system and cytokines can be complicated to navigate, and the path to mitigating them can be a tricky one, too. Here, we take a more detailed look at cytokines: What they are, what they do, and how to keep them in check.

What Are Cytokines?

“Cytokines are small signaling agents generated by cells to facilitate cell-to-cell communication, a primary way in which immune cells talk to each other,” says Dr. Rawls. The term “cytokine” is a blanket term and encompasses many different kinds of crucial chemical messengers.

Cytokines may be derived from proteins, peptides (compounds composed of amino acids, the building blocks of protein), or glycoproteins (a protein molecule with a carbohydrate attached to it). The word “cytokine” originates from two Greek terms:

  • “Cyto,” indicating a cell
  • “Kinos,” meaning movement

These chemical messengers direct the movement of immune cells toward areas of concern in the body, such as infections, trauma, and inflammation, to regulate the immune system.

Types of Cytokines

Some cytokines are anti-inflammatory and encourage healing, while others are pro-inflammatory and worsen symptoms associated with conditions like Lyme disease, autoimmune diseases, and illness or injury. Together, the interplay between the various types of cytokines is aimed at balancing the inflammatory response in the body.

An activated T helper cell segregates the cytokines IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13, leading to B cell antibody class switching,  activation of cytotoxic T cells, and maximazing the bactericidal activity of phagocytes such as macrophages. Source: PDB entries 2B8U, 3VA2, 1ALU, 2H24, 3BPO

Cytokines have other names as well — names specific to the types of cells involved in making them or the action for which they are responsible, according to an article in the medical journal International Anesthesiology Clinics. The other names include:

  • Lymphokine (produced by lymphocytes, a type of small white blood cell)
  • Monokine (generated by monocytes and macrophages, large white blood cells)
  • Chemokine (possess chemotactic activities to activate and migrate other cells of the immune system)
  • Interleukin (produced by leukocytes, a type of blood cell that’s part of the immune system)

Within these classifications of cytokines are individual chemicals that are well known to elevate inflammation in the body. Some of these may be familiar to you:

  • Interleukin-1 (IL-1): A highly inflammatory chemical, IL-1 activates T cells, raises body temperature, works in tandem with other cytokines, and prepares the body to fight disease.
  • Interleukin-12 (IL-12): IL-12 plays a role in regulating the immune system’s natural killer (NK) cells and T cells.
  • Interleukin-18 (IL-18): IL-18 is a binding protein that helps to activate T cells and NK cells and modulate the immune system.
  • Tumor Necrosis Factor (TNF): A protein that helps support the immune system’s response to foreign or toxic substances, TNF may also be responsible for cell death (necrosis) of certain types of tumor cells.
  • Gamma-interferon (IFN-gamma): IFN-gamma is a glycoprotein that helps the body defend against a variety of pathogens such as bacteria, viruses, and protozoa.
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF): Another glycoprotein, GM-CSF can stimulate the production, activation, survival, and differentiation of a variety of immune cells.

Lyme Disease and Cytokines

If this all seems pretty technical, that’s because it is. The duties carried out by the immune system are complex and intricate.

But when it comes to cytokines and Lyme disease, it’s essential to remember that cytokine activity is driven by invaders in the body, says Dr. Rawls. Things like stealth microbes, mold, and toxins are prime culprits that can perpetuate symptoms and disrupt immune system functions. Indeed, the root of many Lyme symptoms can be attributed to an overproduction of cytokines.

For example, a 2017 study in the Journal of Neuroinflammation evaluated the presence of cytokines in individuals with neurological Lyme disease (Lyme neuroborreliosis or LNB). The study notes that the symptoms of LNB included head and neck pain, fatigue, fever, vertigo, radiculitis (inflammation of the nerve root), cranial nerve palsy, and more.

Caucasian girl wake up with neck pain

Samples of cerebrospinal fluid were obtained for individuals with “possible” LNB and those without LNB. The result? Higher levels of cytokines were noted in the cerebrospinal fluid of those with LNB, which may be associated with slower rates of recovery.

This study illustrates one example of the connection between cytokines and Lyme disease. But neurological symptoms aren’t the only ones you might experience when cytokines run amok. You may notice:

  • Fevers
  • Muscle and joint pain
  • Fatigue
  • Poor sleep
  • Cognitive problems
  • Depression, anxiety, or other mental health conditions
  • Hormone imbalances
  • Loss of muscle mass
  • Autoimmune disease

Furthermore, in response to Lyme treatment, many people endure an influx of cytokines. As Borrelia and coinfections like Bartonella and Babesia begin to die off, patients experience Herxheimer (Herx) reactions, or a flood of inflammatory cytokines that occur from antibiotic or herbal therapies. As parts of dead bacteria known as endotoxins circulate throughout the body, the immune system shifts into gear and creates more cytokines to ready itself in defense against infections, trauma, and inflammation. “In abundance, cytokines make you feel terrible,” says Dr. Rawls.

But is it really possible to tame cytokines? Therapies and lifestyle changes aimed at supporting immune health and decreasing inflammation can point you in the right direction.

How to Reduce Proinflammatory Cytokines

Remember that many of the symptoms associated with Lyme disease are due to an excess of proinflammatory cytokines. Here are some ways to decrease them:

1. Shore Up Your Reserves of Vitamin D.

Nicknamed the “sunshine vitamin,” vitamin D is essential for proper immune function, and your body produces it in the skin when exposed to UV light rays. Research suggests sufficient amounts of vitamin D may inhibit the expression of proinflammatory cytokines and boost those that are anti-inflammatory.

However, as many activities have shifted to indoors, the majority of people no longer get adequate sun exposure and are prone to vitamin D deficiencies. So how much do you need?

Vintage alarm clock on the textured brown surface and sun rises, sunny morning, concept of time management

“Thirty minutes to an hour of sun each day on your arms, chest, and face (without sunscreen) should be enough to keep your vitamin D levels in a healthy range,” advises Dr. Rawls. The optimal hours to catch some rays are between 10 am and 2 pm.

However, some people may require supplemental vitamin D3 to augment their levels. Dosages ranging from 1,000 IU to 4,000 IU are sufficient for most people, but the amount you need can vary based on your geographic location and skin tone. If you’re uncertain whether you’d benefit from a vitamin D supplement, ask your doctor for a simple blood test to check your levels.

2. Boost Your Intake of Turmeric.

With its unmistakable orange-yellow color, turmeric is the spice that’s most often associated with Indian curry. But turmeric is more than just a colorful cooking spice. It’s been used in Ayurvedic medicine for thousands of years, and it’s a potent anti-inflammatory herb with the power to mitigate cytokines.

In addition to its pain-relieving properties, turmeric may be useful for digestive disorders, protecting liver cells, decreasing the risk of dementia, and reducing arthritis symptoms. For most people, turmeric tends to be well-tolerated, and side effects are rare.

3. Consider Adding CBD.

CBD, short for cannabidiol, is a non-psychoactive chemical component from hemp. It’s been touted for its ability to reduce pain, lessen seizures, improve mood and sleep, protect the nervous system, and more. And with good reason! Research indicates CBD may suppress cytokine activity and other inflammatory responses.

Clinical trials involving animals and humans have shown CBD to be extraordinarily safe. Though uncommon, side effects may include feeling tired, loose stools, and mild changes in appetite or weight.

4. Up Your Detox Game.

Both pathogens and their toxins can contribute to the production of bothersome cytokines, especially when you’re on a treatment protocol aimed at killing microbes, or you experience a herx. The higher the infectious and toxic loads in your body, the more likely your detoxification pathways are already overwhelmed.

To improve Lyme symptoms and subdue an overactive cytokine response, you may need to up your detox game. There are many ways to do so, but some top choices to lessen cytokines include using an infrared sauna, taking a toxin binder like chlorella or activated charcoal, and engaging in mild exercise.

5. Implement Ways to Reduce Stress.

In addition to infections and toxins, cytokines can also result from being in flight-or-fight mode from chronic stress, notes Dr. Rawls. As stress continues to take a toll on your body, the consequent inflammation can impact your brain and nervous system, according to a review in the journal Frontiers in Human Neuroscience.

Office worker typing email on tablet computer. The woman feels stressed and nervous, holds an antistress yellow ball in her hand

Although you’ll never rid your life of stress completely, working to minimize it as best as you can only serves to combat cytokines and, ultimately, reduce your symptoms. There are many excellent ways to cut down on stress; we tend to favor ones that are cost-effective and easily accessible, such as:

  • Journaling
  • Taking a leisurely walk in nature
  • Doing restorative yoga
  • Practicing meditation
  • Relaxing in a warm bath

Pick whichever stress-reducing activities resonate with you most, and do your best to stick with them to help reestablish your sense of calm.

There’s no doubt that the concept of cytokines can be a challenging one to grasp. These chemical messengers send our immune system a myriad of important signals, and keeping them in balance is vital to improving your health.

To dampen excess proinflammatory cytokines, take steps to lower inflammation, support immune health, and find ways to manage chronic stress. Though it may take some time and patience, you’ll begin to experience less symptomatic days and have a better quality of life.

Dr. Rawls is a physician who overcame Lyme disease through natural herbal therapy. You can learn more about Lyme disease in Dr. Rawls’ new best selling book, Unlocking Lyme.
You can also learn about Dr. Rawls’ personal journey in overcoming Lyme disease and fibromyalgia in his popular blog post, My Chronic Lyme Journey.


1. Calton EK, Keane KN, Newsholme P, Soares MJ. The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies. PLoS One. 2015;10(11):e0141770. Published 2015 Nov 3. doi:10.1371/journal.pone.0141770
2. Cavaillon JM. Pro- versus anti-inflammatory cytokines: myth or reality. Cell Mol Biol (Noisy-le-grand). 2001;47(4):695‐702.
3. Dinarello CA. Interleukin-1. Cytokine Growth Factor Rev. 1997;8(4):253‐265. doi:10.1016/s1359-6101(97)00023-3
4. Dinarello CA. Interleukin-18. Methods. 1999;19(1):121‐132. doi:10.1006/meth.1999.0837
5. Dinarello CA. Proinflammatory cytokines. Chest. 2000;118(2):503‐508. doi:10.1378/chest.118.2.503
6. Ferreira VL, Borba HH, Bonetti ADF, Leonart LP, Pontarolo R. Cytokines and Interferons: Types and Functions. Autoantibodies and Cytokines. 2019. doi:10.5772/intechopen.74550
7. Gyllemark P, Forsberg P, Ernerudh J, Henningsson AJ. Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study. J Neuroinflammation. 2017;14(1):27. Published 2017 Feb 1. doi: 10.1186/s12974-017-0789-6
8. Li H, Kong W, Chambers CR, et al. The non-psychoactive phytocannabinoid cannabidiol (CBD) attenuates pro-inflammatory mediators, T cell infiltration, and thermal sensitivity following spinal cord injury in mice. Cell Immunol. 2018;329:1‐9. doi:10.1016/j.cellimm.2018.02.016
9. Liu YZ, Wang YX, Jiang CL. Inflammation: The Common Pathway of Stress-Related Diseases. Front Hum Neurosci. 2017;11:316. Published 2017 Jun 20. doi:10.3389/fnhum.2017.00316
10. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033‐1034. doi:10.1016/S0140-6736(20)30628-0
11. Tau G, Rothman P. Biologic functions of the IFN-gamma receptors. Allergy. 1999;54(12):1233‐1251. doi:10.1034/j.1398-9995.1999.00099.x
12. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995;13:251‐276. doi:10.1146/annurev.iy.13.040195.001343
13. Yadav R, Jee B, Awasthi SK. Curcumin Suppresses the Production of Pro-inflammatory Cytokine Interleukin-18 in Lipopolysaccharide Stimulated Murine Macrophage-Like Cells. Indian J Clin Biochem. 2015;30(1):109‐112. doi:10.1007/s12291-014-0452-2
14. Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45(2):27‐37. doi:10.1097/AIA.0b013e318034194e