What Is Type 2 Inflammation and What Conditions Does It Cause?

Inflammation is the body’s natural process of fighting against injury and foreign invaders, a protective mechanism designed to initiate healing. However, this process is not a single reaction, as scientists have identified distinct inflammatory responses. This article explores Type 2 inflammation, a pathway that, while beneficial in some contexts, is also the underlying cause of several chronic and often debilitating conditions.

Type 1 vs. Type 2 Immune Responses

The immune system has different ways of responding to threats, categorized into two main pathways: Type 1 and Type 2 immunity. The Type 1 response is primarily geared towards eliminating intracellular pathogens, such as viruses and certain bacteria that replicate inside the body’s cells. This pathway involves activating immune cells specialized to recognize and destroy these infected cells.

In contrast, the Type 2 immune response evolved to combat larger threats that cannot be engulfed by a single immune cell, such as parasitic worms. This pathway stimulates antibody production and activates a different set of immune cells. With large parasitic infections now rare, this Type 2 pathway is more frequently activated inappropriately in response to harmless substances known as allergens, like pollen or certain foods, leading to allergic diseases.

Key Drivers of Type 2 Inflammation

The Type 2 inflammatory response is orchestrated by messenger proteins called cytokines. Three of these cytokines, Interleukin-4 (IL-4), Interleukin-5 (IL-5), and Interleukin-13 (IL-13), are important in driving this type of inflammation. IL-4 and IL-13 stimulate B cells to produce a specific type of antibody and contribute to features like increased mucus production.

These cytokines mobilize a specialized team of immune cells. IL-5 is particularly effective at recruiting and activating cells known as eosinophils, a type of white blood cell that contributes to tissue inflammation. Mast cells and basophils are other cellular players that, when activated, release substances like histamine, which causes many immediate allergic symptoms.

A component linking these elements is an antibody called Immunoglobulin E (IgE). In response to an allergen, the Type 2 pathway, driven by IL-4 and IL-13, increases IgE production. This IgE then attaches to the surface of mast cells and basophils. When the body encounters the same allergen again, it binds to the IgE on these cells, triggering them to release their inflammatory contents.

Conditions Caused by Type 2 Inflammation

The persistent and misdirected activity of the Type 2 inflammatory pathway is the underlying cause of several chronic diseases. These conditions may appear distinct, but they share this common biological origin, and it is not uncommon for an individual to have more than one of them.

• Asthma: In the airways, this inflammation causes passages to swell, increases mucus production, and tightens surrounding muscles, resulting in coughing, wheezing, and difficulty breathing.
• Atopic Dermatitis (Eczema): This is the manifestation of Type 2 inflammation in the skin, where the process disrupts the skin’s natural barrier, leading to dry, itchy, and inflamed rashes.
• Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): This inflammatory cascade affects the upper airways and sinuses, causing persistent inflammation that leads to the growth of soft swellings called polyps.
• Eosinophilic Esophagitis (EoE): In the digestive system, eosinophils accumulate in the esophagus, causing inflammation that can make swallowing difficult and painful.
• Food Allergies: This process is central to many food allergies, where the IgE-mediated response to certain foods triggers reactions ranging from mild to severe.

Diagnosis and Targeted Treatments

Identifying whether Type 2 inflammation is driving a patient’s condition involves clinical evaluation and specific tests. A personal or family history of allergic diseases can be an initial clue. A common diagnostic tool is a complete blood count (CBC) to check for elevated levels of eosinophils in the blood.

Other tests include measuring the total level of IgE antibodies in the blood and conducting skin prick tests to identify specific allergens. For asthma, a test that measures fractional exhaled nitric oxide (FeNO) can also serve as a biomarker, as higher levels can indicate Type 2 airway inflammation.

Understanding the molecules that drive this pathway has led to the development of highly specific medications known as biologics. These treatments are a more precise approach than general anti-inflammatory drugs. They are designed to target and block components of the Type 2 cascade, such as the cytokines IL-4, IL-5, and IL-13, or the IgE antibody itself. By neutralizing these drivers, biologics can interrupt the inflammatory cycle and reduce symptoms.