An Overview of Type 2 Inflammation

Type 2 inflammation is a specific type of immune response pattern. It can have positive effects, like helping eliminate a parasitic infection. But it also plays a role in certain medical conditions, such as atopic dermatitis (eczema), allergic rhinosinusitis, and some types of asthma.

Some new therapies, like Dupixent (dupilumab), work by combating type 2 inflammation.

What Causes Type 2 Inflammation?

The immune system has different strategies to deal with different kinds of pathogens. The way to target and kill a bacteria or virus is not the best way to eliminate a parasite such as a worm. So the immune system has different components that eliminate and prevent infections in different ways. 

Type 2 immune activation is one pattern of activation that the immune system can use.

T Cells

To understand type 2 inflammation, we need to consider a specific type of immune cell called a T cell. Other parts of the immune system (like parts of the innate immune system) may be important for triggering this type of inflammation, but T cells play a key role.

T cells become activated by other types of immune cells to recognize specific pathogens. After that happens, some of those cells undergo further changes to become what are called T helper cells (“Th” cells).

T helper cells play a key role in coordinating the immune response. They do this through releasing specific immune-signaling molecules, called cytokines. These cytokines then influence the activity of a variety of other cells in the immune system to act in specific ways.

Based on the signaling and activation they’ve received from other immune cells, the T helper cells can start to generate one of two overarching types of immune response. Overall, a Th1 type response (or type 1 inflammatory response) is better at producing an immune response that is effective at targeting viruses and bacteria.

In contrast, a Th2 type response is better at eliminating certain parasites, like tapeworms or nematodes.

During a Type 2 Immune Response

During a type 2 inflammatory response (Th2 response), T helper cells release cytokines such as IL-4, IL-5, IL-9, and IL-13. The Th2 response also promotes the formation of a specific type of antibody, termed IgE antibodies. 

Specific immune cells called mast cells, basophils, and eosinophils get activated. These cells do things like help secrete mucus, promote swelling, contract smooth muscle cells, and release particles that could destroy a parasite. In the case of an active infection, all these responses can help rid your body of the invading parasite.    

Abnormal Type 2 Inflammation

A Th2 type immune response can be very helpful in fighting some kinds of infections. However, sometimes this type of immune response can become hyperactivated and not well regulated. 

Too many T cells may start to become activated by the Th2 signaling pathway. Some may stay active for far too long. Some Th2 cells may turn into memory cells that stick around for a long time and cause long-term changes in the immune response.

This can lead to serious inflammation, which may be retriggered at some point in the future. When the Th2 pathway is dysregulated in this fashion, it is more often referred to as type 2 inflammation. 

For complex reasons, sometimes this inflammatory pathway can be activated by things that aren’t infectious. The pathway can get triggered, even though there isn’t anything to fight. 

If an immune system has been over-sensitized, it might start responding with severe type 2 inflammation to a trigger like pollen, animal dander, dust, or certain foods. In other words, the substance can trigger a type of allergic response, one caused by hyperactivation of the Th2 pathway. 

Diseases Partly Caused by Type 2 Inflammation

This type 2 inflammatory response plays a key role in multiple different medical illnesses. Many of the details are still being worked out by researchers.

Type 2 Inflammation in Atopic Diseases

Type 2 inflammation clearly plays a role in diseases that can all be exacerbated by certain environmental allergic triggers. These are also called “atopic” diseases. 

These diseases are closely related. Individuals who have one of these problems are more likely to have an additional problem in this group than someone in the general population.

Some of the diseases of this type include:

• Atopic dermatitis (commonly called eczema)
• Chronic rhinosinusitis (sometimes with nasal polyps; CRSwNP)
• Asthma
• Chronic spontaneous urticaria

However, it’s a little more complicated than that. For example, in some people with asthma, type 2 inflammation seems to be playing a much greater role than in other people.

About 70% to 80% of people with asthma seem to have type 2 inflammation as a major contributing cause. This is sometimes called allergic asthma to distinguish it from asthma that doesn’t have type 2 inflammation as an underlying cause.

The type 2 inflammatory pathway is also involved in life-threatening anaphylactic allergic reactions. For example, some people have such reactions to peanuts, bee stings, or other triggers.

Type 2 Inflammation in Autoimmune Disease

Exaggerated type 2 inflammation may also be playing a role in some autoimmune diseases, such as multiple sclerosis. Researchers have been studying the type 2 inflammatory pathway in these diseases, and exaggerated type 2 inflammation may be important. 

However, this is not as clear cut as it is for diseases with a known allergic component (like asthma). In traditional autoimmune disease, both exaggerated type 2 and type 1 inflammation may be part of the problem.

Type 2 Inflammation Pathway Treatments

Researchers have developed therapies to target different parts of the type 2 inflammation pathway. Most of these treatments work by blocking the immune signaling molecules that get this type of inflammation going. 

Several different therapies have been approved by the FDA to treat allergic asthma. These aren’t used as sole treatments. Instead, they are usually used in addition to other therapies in people who still have significant symptoms. Some of these are:

• Xolair (omalizumab): Depletes IgE antibodies
• Nucala (mepolizumab): Blocks IL-5
• Cinqair (reslizumab): Blocks IL-5
• Dupixent (dupilumab): Blocks IL-4 and IL-13

Some of these therapies are also FDA approved for other medical conditions affected by type 2 inflammation. For example, Dupixent is also approved for moderate to severe atopic dermatitis (eczema) as well as chronic rhinosinusitis with nasal polyps.

As another example, Xolair has also received FDA approval to treat chronic spontaneous urticaria.

Because these diseases share some underlying causes—increased type 2 inflammation—it’s not surprising that some of these therapies might be successfully used for more than one type of medical condition.

Therapies Under Investigation

Several therapies targeting the type 2 inflammatory pathway are at various stages of scientific development. Some of these are therapies that haven’t yet been approved for any disease. But others are therapies currently being used for other diseases worsened by type 2 inflammation. 

For example, scientists are evaluating the effectiveness of Dupixent in treating medical conditions such as the following, which are also thought to have type 2 inflammation as a contributing cause: 

• Allergic contact dermatitis
• Alopecia
• Chronic obstructive pulmonary disease (COPD) subtype with type 2 inflammation
• Eosinophilic esophagitis

Some of these might eventually receive official FDA approval.

New therapies working on the type 2 inflammation pathway also might become approved. For example, tralokinumab is a therapy designed to block IL-13. It hasn’t yet received approval by the FDA to treat any disease. But it is currently being reviewed for possible approval for atopic dermatitis (eczema) later in 2021.