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Pulmonary Fibrosis: The Mast Cell & Histamine Connection

There is a lot to get excited about when we look at mast cell involvement in pulmonary fibrosis (PF). Lungs are one of the places in the body where an abundance of mast cells can be found.

PF is a lung disease where scarring (fibrosis) makes it difficult to breathe. As the scarred tissue becomes thicker and stiffer, breathing becomes more and more difficult. Treatment can include drugs that slow the progression of the disease, oxygen therapy or pulmonary rehab.

Sometimes a lung transplant is appropriate and can allow a person to live longer.

You might think it thoughtless of us to get excited about such a debilitating chronic health condition, but when you understand the mast cell piece, it means you have new possibilities to address what is underlying this condition.

Mast Cells in the Lungs

Mast cells in the lungs play a role in the integrity of the lung tissue, in immune regulation and microbial defense when you breathe in viruses or bacteria, and in tissue repair if your lungs get damaged.

Injury or damage to the lungs can result from a variety of reasons. Breathing in toxins found in dusts from coal, metals, grains (farming), glyphosate, or asbestos can trigger this condition. Mold spores are another possible source of toxins that cause damage.

Lung Damage

Infections can damage lung tissue (1) . Epstein-Barr and herpes virus 8 (2) are some of the infections correlated to PF. Lyme disease may also be a potential trigger (3).

Connective tissue autoimmune conditions such as rheumatoid arthritis, scleroderma, or sarcoidosis can also be a factor leading to the lung injury that can trigger PF. Certain drugs are known to induce damage as well. (4)

Research reveals that there is an accumulation of mast cells in fibrosis (5). In PF, these mast cells release many compounds such as interleukins (IL-3, IL-4, IL-5, IL-6, IL-13), growth factors (fibroblast growth factor, platelet derived growth factor, tumor growth factor, vascular

endothelial growth factor) and other pro-fibrotic chemical mediators contributing to the development of the fibrosis. (6)

Histamine is another mediator that contributes to the formation of fibrosis. (7)

A mast cell response is a normal, healthy response to repair damaged or injured tissue.

However, it appears that with PF, mast cells are activated on an ongoing basis, contributing to the formation of fibrosis.

The Overlap and The Evidence

Toxins and infection are known triggers for mast cell activation. (Read a good primer on these here.) Infections are also known to trigger mast cell activation. (Read more on this topic here.) Did you notice that these known triggers overlap with the causes of lung injury associated with PF?

Another overlap exists when we look at comorbidities associated with PF. These conditions are also known to have mast cell involvement:

Interestingly, the drugs used to slow the progression of PF have effects on mast cells or their mediators. Nintedanib (sold under brand names Ofev and Vargatef ) inhibits c-kit receptors on mast cells inhibiting kinase release (8).

The drug called Pirfenidone (sold under brand name Esbriet) reduces TNF and IL-1β (mast cell mediators) in inflammatory lung conditions (9) and it inhibits TGF-β (10), a pro-fibrotic growth factor.

Hypoxia is one more trigger of mast cell activation (Read a good primer on this here.) Hypoxia is a characteristic of PF, but interestingly this feature also further elevates fibrotic mediators. (11)

Does this create a vicious cycle? Is the hypoxia induced by fibrosis, further activating mast cells?

Were mast cells already activated elsewhere in the body, and PF is another manifestation of a systemic problem?

At this point there doesn’t seem to be an answer to these questions, but what is clear is that mast cells are releasing chemical mediators that contribute to the formation of the fibrosis (scarring).

One Question that Can Been Answered

Should mast cells stabilization be part of PF therapy?

We aren’t the only ones who answer YES to this question.

A study published in 2020 also suggests that mast cell stabilization should be used with PF (read more here). This study highlights some of the flavonoids found in foods such as quercetin, luteolin and crysin, as well as drugs that stabilize mast cells. Watch for another blog post later this month where we will focus on some of these important flavonoids!

What If?

What if, in addition to pharmaceuticals, you could use food and lifestyle factors to stabilize mast cells and slow down the release of the chemicals that are contributing to fibrosis formation?

That’s what Histamine Haven is here for. Our goal is to help you calm your mast cells. Please share this article with anyone you know who has pulmonary fibrosis.

Watch for our next blog, (+ sign up to get our notifications!) where we’ll be sharing a great dietary tip to help stabilize those mast cells.

Let's help you build safety on your dinner table, one meal at a time!


If you or a loved one have the diagnosis, join us for the next The Histamine Connection.

It's a free class, and it's happening online. This class is to help you make that histamine connection for yourself, and to get you started with 3 important tips to reduce histamine via foods. When you do this, you slow down what is potentially driving your symptoms!

Our next class will focus on respiratory and lung connected issues, but we will tie it in to other symptoms and systems of the body as well. Everyone is welcome!

Jot it in your calendar: Thursday February 23rd, 7pm Mountain Time (Alberta / Santa Fe / GMT -6). Register here for this free Histamine Connection class.

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