18. Welcome back! Dr. Theoharides tells us about mast cells and neuroinflammation

Dr. Theoharis Theoharides, Professor of Immunology at Tufts University School of Medicine in Boston and Sarah Cormode talk on Looking at Lyme, Season Two!

Welcome back to Season 2 of the Looking at Lyme podcast. Buckle your seatbelts, because we are going on a science adventure with Dr. Theoharis Theoharides, Professor of Immunology at Tufts University School of Medicine in Boston. Dr. Theoharides has been on the leading edge of mast cell research and recounts the fascinating history and physiology of mast cells. Mast cells have existed for over a hundred million years in many different animals and organisms and are found in all body tissues, including the brain.

Mast cells are found in worms, fish, lizards; however, these species do not get allergic reactions. So why are mast cells associated with allergic reactions?

Dr. Theoharides explains that mast cells became associated with allergies in 1947 when it was discovered that they contained histamine. He describes the activation of mast cells during anaphylaxis as the sudden release of about 50 molecules from inside these cells, followed by a delayed release 6-12 hours later of further, newly synthesized molecules. He reflects on his earlier research showing that the release of these molecules can also occur, not only with allergies, but also due to many pathogenic, environmental triggers (for example, mold), and stress hormones. He notes that triggers such as Borellia or mold can cause the release of only cytokines (not histamine, or tryptase) from the mast cells. Dr. Theoharides also explains that when mast cells are “primed” with interleuken 33, followed by stress hormone release, the mast cells can release more pro-inflammatory cytokines than any other type of immune cell. This massive release of cytokines is referred to as a “cytokine storm”. 

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“I think we (and colleagues) have been missing the forest for the trees, by looking at the mast cell involvement in allergy and missing the mast cell involvement in neuro-inflammatory processes, especially those that worsen by stress.”

Dr. Theoharis Theoharides

Dr. Theoharides explains that while mast cell activity in the lungs leads to asthma, the role of mast cells on neuroinflammation of the brain is due to a more complex process. He notes that in other parts of the body, the immune response involves immunoglobulin E, but in the brain microglia are the basis of its defense. When activated by toxins or microbes that enter the brain, the microglia engage an immune response which includes the release of inflammatory cytokines. He notes that the areas of the brain that regulate homeostasis and emotion have more mast cells than we have in our skin. These mast cells are not activated in the same way as other parts of the body, but may be activated by toxins such as glyphosate as well as heavy metals such as mercury.  

Dr. Theoharides points to more recent research regarding what is now known as Mast Cell Activation Syndrome (MCAS), which is seen in patients who have an increased amount of mast cells in the body, or increased activation of mast cells. He goes on to describe how mast cells in blood vessels of the brain, when activated, can lead to a disruption of the blood-brain barrier. When toxins and other molecules enter the brain, the microglia become activated. The release of cytokines from the mast cells, along with the toxins and other particles results in localized inflammation to certain areas in the brain. In light of these reactions in the body, Dr. Theoharides cautions against therapies that may increase immune activity. He briefly comments about testing and treatments to remove heavy metals in the body such as chelation.

“So imagine the microglia [in the brain] all of a sudden seeing molecules coming from the mast cells, toxins coming from the blood…and immune cells – they literally go wild. So what you have is something like the clones in Star Wars.”

Dr. Theoharis Theoharides

The CDC recently recognized Multisystem Inflammatory Syndrome as a cluster of symptoms experienced by some COVID-19 patients. Dr. Theoharides notes the similarity between this syndrome (MIS-A in adults and MIS-C in children), the experience of Lyme patients and Mast Cell Activation Syndrome (MCAS). In the case of COVID-19, he points to the potential for natural molecules such as Quercetin and Luteolin to help manage the disease. He notes that several research studies have shown the usefulness of these molecules and are being considered management of COVID-19 in Canada and the US. In the absence of universal treatment options, he questions the ethics of not using these natural molecules to reduce symptoms of the COVID-19 virus. Dr. Theoharides encourages listeners to seek out supplements that are high in quality, purity and are produced with good manufacturing practices. He refers listeners to his website, mastcellmaster.com, for further information, research and videos.


“Much of what we’ve done over the last few years now has been picked up within the COVID-19 arena as well.”

Dr. Theoharis Theoharides
Dr. Theoharis Theoharides, Professor of Immunology at Tufts University School of Medicine in Boston and Sarah Cormode talk on Looking at Lyme, Season Two!

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