Mast cell activation interplay between immunity, neuroinflammation

It’s hard not to be obsessed with mast cells, said Tania Dempsey, MD, ABIHM, at the 2022 Integrative Healthcare Symposium in New York City.

“They’re so important while treating our patients with multi-system symptoms.”

Mast cells are widespread in the human body and have a diverse array of functions according to Dempsey, founder of Armonk Integrative Medicine Center for Personalize Medicine in Purchase, New York. They're heterogeneous, meaning they function differently depending on their location in the body. Mast cells are found in most tissue and organs, concentrating more densely in areas in close contact with the environment such as the skin, airways and the gastrointestinal (GI) tract to help with early recognition of pathogens.

Mast cells play an important role in the innate immune system, Dempsey said. As one of the first lines of defense against a foreign substance, mast cells release chemicals. These chemicals are known as mediators and they kill pathogens. After this release, a normal mast cell will return to their normal state and wait for the next attack. An abnormal mast cell, on the other hand, will continue to attack when there’s no infection. This phenomenon is known as Mast Cell Activation Syndrome (MCAS). Dempsey explained that MCAS is when cells release their mediators inappropriately, which in theory, causes the cells to be progressively more dysfunctional.

What’s less commonly known, said Dempsey, is that mast cells also are found in the nervous system. They reside near nerve fibers and neuroglia where they’re able to modulate neural activity and nociception interacting bi-directionally. Mediators from the mast cell prompt the release of neuropeptides from nerve endings, further activating the mast cell. This interplay can contribute to worsening neuroinflammation.

In addition to inflammation in the nervous system, the effects of MCAS can be seen throughout the body with an array of symptoms including rashes, bloating, nasal congestion, and bone pain, making the condition not only difficult to treat, but to diagnose, according to Dempsey.

Overall, Dempsey said symptoms of MCAS fall into one or more of three categories—the allergic type phenomena, the inflammatory phenomena, and an aberrant growth and development. 

“People think mast cells are only involved in allergy, but there’s so much more," said Dempsey.

The inflammatory phenomena can manifest throughout the body whether it’s in the GI tract or the peripheral nerves. Mast cells help in the regeneration of tissue, so when their dysfunctional symptoms such as growths and tumors may present themselves falling under the aberrant growth and development category.

The diagnosis of MCAS requires specialized labs and processing of blood and urine. According to Dempsey, if practitioners suspect their patient has MCAS, whether its because their symptoms, or they’re not responding to traditional interventions, often it’s best to refer patients out to a specialist.

Once a patient has been diagnosed, Dempsey said MCAS treatment should begin with looking at the patient and their body as a whole. She listed several pharmacologic treatments as well as non-pharmacologic, noting that the list is ever-growing. Some of the pharmacologic treatments included H1 blockers, H2 blockers, leukotriene inhibitors, Aspirin, corticosteroids, and mast cell stabilizers. Dempsey’s list of non-pharmacologic treatments included a low histamine diet, vitamin C, diamine oxidase enzyme, and alpha lipoic acid.

Dempsey said each of these treatments had pros and cons. For example, a low histamine diet can be confusing and inconvenient for patients to follow. She said the trick to treating MCAS is looking at the body as a whole, addressing the many nuanced symptoms that come with MCAS with a multi-treatment, integrative approach.

“You can’t predict who is going to reaction to a treatment or in what way. It’s frustrating but you just have to have patience,” said Dempsey.

Editor's note: This article is part of Integrative Practitioner's live coverage of the 2022 Integrative Healthcare Symposium at the Hilton Midtown in New York City. Click here to catch up on the live coverage.