What Is Type 2 Inflammation?

Type 2 inflammation is a specific immune response that happens throughout the body. It fights against parasitic infections, in particular parasitic worms.

But in some cases, the type 2 inflammation response can be triggered by things other than parasitic infections. It may be triggered by exposure to an allergen, such as a certain food, an environmental allergen, or something that contacts the skin. The immune system sees this as a threat and mounts an attack. Immune cells get activated, which starts the inflammatory process.

This overactive type 2 inflammatory response is associated with several health conditions, such as asthma, atopic dermatitis, and eosinophilic esophagitis (EoE).

In type 2 inflammation, activated immune cells include:

• type 2 innate lymphoid cells (ILC2)
• type 2 helper T cells (Th2)

Those cells react by releasing proteins called interleukins (IL). Specifically, IL-4, IL-5, and IL-13 are part of the type 2 inflammatory pathway. Effective treatments for type 2 inflammatory conditions target those proteins to block their actions in the body.

These inflammatory cells produce high levels of IgE, one of the antibodies involved in the allergic response.

Specific immune cells involved in allergic inflammation also become activated, including:

• mast cells
• basophils
• eosinophils

The inflammatory cells released by the immune system create a variety of changes in the body. In type 2 inflammation, it’s mainly the skin, lungs, and airways that are affected. Some parts of the digestive tract may also be involved.

Signs and symptoms of type 2 inflammation include:

• an increase in mucous secretion
• swelling in the airways and nasal passages
• difficulty breathing, wheezing, or chest tightness
• coughing
• narrowing of the esophagus
• red and itchy skin

Type 2 inflammation is caused by a specific series of immune responses. Our immune system is designed to target harmful invaders.

A type 2 inflammatory response is designed to fight off parasites such as worms. Sometimes it overreacts to something that wouldn’t typically be a threat. Allergens such as dust, pollen, or dander can trigger type 2 inflammation. This is the underlying cause of several health conditions.

Type 2 inflammatory conditions share a specific immune response. Many people live with more than one type 2 inflammation-related condition.

For example, among people with moderate to severe asthma, 60% also have allergic rhinitis, and 15% have atopic dermatitis.

Here are some of the health conditions related to type 2 inflammation.

Atopic dermatitis

Atopic dermatitis is a type of eczema. It’s an inflammatory skin condition that causes itchy, inflamed, or dry patches of skin. In people with lighter skin tones, these patches may appear red. In people with darker skin tones, they may appear dark brown, purple, or ashen gray.

High levels of IL-4 and IL-13 are seen in people with atopic dermatitis. This shows that the type 2 inflammatory pathway is active in this skin condition. Atopic dermatitis often starts in childhood. Children with atopic dermatitis often develop other allergic conditions, such as asthma and food allergies.

Asthma

Asthma is a condition that affects the lungs and airways. When airways get inflamed, it can be harder to breathe. Asthma causes wheezing, tightness in the chest, shortness of breath, and coughing.

Not all people with asthma experience type 2 inflammation as part of their condition. According to research, type 2 inflammation affects up to 51% of people with uncontrolled asthma and 55% to 70% of people with severe asthma. People with type 2 inflammation in their airways are more likely to have asthma flares.

Chronic rhinosinusitis with nasal polyps (CRSwNP)

Chronic rhinosinusitis is inflammation in the nose and airways that lasts more than 12 weeks. It can be present with or without nasal polyps. Nasal polyps develop due to high levels of inflammation in the nose. These polyps occur in about 20% of patients with chronic rhinosinusitis.

One study found that among people with moderate to severe CRSwNP, type 2 inflammation was present in 69% of patients.

Eosinophilic esophagitis

EoE is a condition that affects the esophagus. White blood cells called eosinophils build up in the esophagus. This causes inflammation and can cause the esophagus to narrow, which can lead to swallowing difficulties.

Type 2 inflammation causes a rise in eosinophil levels. It can also cause eosinophils to be present in places they wouldn’t normally be, such as the esophagus.

Chronic idiopathic urticaria

Chronic idiopathic urticaria is a term for hives that have no known cause and last for at least 6 weeks. The hives can develop on almost any part of the body.

There are many different immune pathways that can cause hives. Type 2 inflammation is responsible for some cases of chronic idiopathic urticaria. One clue is the presence of white blood cells called eosinophils in the tissue affected by hives and swelling. This is similar to the allergic response seen in EoE.

The goal of treatment for type 2 inflammation is to block specific proteins released by the immune system. This helps prevent damage from the inflammatory pathway. In turn, this can prevent or lessen symptoms.

Some treatments may be able to help manage more than one inflammatory condition.

Treatments that are used to target the pathways of type 2 inflammation include:

• Steroids: Steroid medications are used to reduce the overall immune response. They’re not as targeted as other medications. They may still help to lower inflammation and improve symptoms.
• Dupilumab (Dupixent): This is a type of biologic medication that targets IL-4 proteins, which are part of the type 2 inflammatory pathway. This medication is approved for use for atopic dermatitis, asthma, EoE, and CRSwNP.
• Omalizumab (Xolair): This is a biologic medication that blocks IgE, an antibody that is part of the allergic response. This medication is approved for asthma, chronic idiopathic urticaria, and nasal polyps.
• Mepolizumab (Nucala) and benralizumab (Fasenra): These are biologic medications that target IL-5 proteins, another part of the type 2 inflammatory pathway. They are approved for use in people with eosinophilic asthma.

You can work with a doctor to help develop a treatment plan for your specific condition and symptoms. You’ll likely have many healthcare professionals as part of your care team. You may work with an allergist, dermatologist, gastroenterologist, or ear, nose, and throat (ENT) specialist.

Type 2 inflammation is a specific immune pathway to protect us from parasites. Sometimes, this same response is triggered by allergens. This causes inflammation throughout the airways and nasal passages. It also shifts IgE antibodies into some of the body’s tissues, causing symptoms in those areas.

This immune response may be related to several health conditions. They include asthma, chronic idiopathic urticaria, eosinophilic esophagitis, chronic rhinosinusitis with nasal polyps, and atopic dermatitis. If you live with one type 2 inflammatory condition, you may be more likely to develop another one.

Some existing medications are found to work for more than one condition. New treatment options target the specific pathways involved in type 2 inflammation.