The human body’s immune system uses a network of protein messengers called cytokines, which function like text messages between cells, to coordinate its defenses and dictate cellular behavior. One messenger, Interleukin-4 (IL-4), is a cytokine with varied effects on many cell types. Discovered in 1982, IL-4 plays a part in processes ranging from immune defense to allergic reactions.
How IL-4 Communicates in the Body
Interleukin-4 is produced by several immune cells, primarily a class of T-helper cells called Th2 cells, as well as by mast cells, eosinophils, and basophils. Once released, IL-4 travels through the body to deliver instructions. The message is received when the IL-4 protein binds to a specific docking station on a target cell, known as the IL-4 receptor (IL-4R). This interaction is highly specific, much like a key fitting into a lock.
This binding event initiates a cascade of signals inside the recipient cell. For the signal to be transmitted, IL-4’s binding to the first part of the receptor, a chain called IL-4Rα, causes another receptor chain to join and form a functional complex. This completed receptor then activates intracellular molecules, such as STAT6, which carries the signal to the cell’s nucleus and directs changes in gene expression.
There are two main versions of the IL-4 receptor, Type I and Type II. The Type I receptor is found on immune system cells, while the Type II receptor is present on non-immune cells, including those in the airways and skin. This distribution allows IL-4 to orchestrate a broad range of biological effects, influencing everything from immune cell development to the contraction of lung muscle cells.
The Connection to Allergies and Asthma
The role of IL-4 is well-documented in the development of allergic diseases, including hay fever, atopic dermatitis (eczema), and asthma. These conditions are driven by a specific inflammatory response known as type 2 inflammation, in which IL-4 is a central player. When an individual with a predisposition to allergies is exposed to a harmless substance like pollen, their immune system can overreact.
A defining action of IL-4 in this process is its effect on B cells, which produce antibodies. IL-4 instructs B cells to undergo a “class switch,” causing them to produce a specific antibody called Immunoglobulin E (IgE). This step is necessary for the large amounts of IgE production that characterize an allergic state.
Once produced, IgE antibodies circulate and attach to the surface of immune cells like mast cells and basophils, priming them for a reaction. IL-4 further amplifies this by increasing the number of IgE receptors on these cells, making them more sensitive. Upon subsequent exposure to the same allergen, it binds to the IgE on these primed cells, triggering them to release inflammatory chemicals like histamine. This causes classic allergy symptoms, and IL-4 also contributes to asthma by inducing excess mucus production in the airways.
A Key Defender Against Parasites
While problematic in allergies, the IL-4-driven immune pathway also serves a protective function. The same type 2 inflammatory response that drives allergies is effective at combating infections by parasitic worms, known as helminths. The mechanisms that cause allergic symptoms are repurposed in this context to physically expel parasites.
When the body detects a parasitic worm infection, immune cells are stimulated to produce IL-4. This triggers the same cascade seen in allergies, but the response is directed at the parasite. The inflammatory environment created by this pathway is hostile to the worms.
The response helps coordinate the physical removal of these parasites. For instance, increased mucus production in the gut can help trap worms, while smooth muscle contractions aid in their expulsion. Eosinophils, another cell type activated in this pathway, release toxic proteins that can directly damage the parasites.
Therapeutic Drugs Targeting IL-4
The understanding of IL-4’s function in allergic diseases has led to modern medical treatments. Since overactive IL-4 signaling causes conditions like atopic dermatitis and asthma, scientists have designed targeted drugs to block its activity, interfering with the specific molecules driving the disease.
These drugs are often monoclonal antibodies, which are laboratory-produced proteins designed to bind to a single, specific target. The target is either the IL-4 cytokine itself or its receptor, IL-4Rα. By binding to this receptor, the drug effectively blocks the “lock,” preventing IL-4 from delivering its inflammatory message.
An example of this therapeutic strategy is the drug dupilumab (Dupixent). This monoclonal antibody is engineered to bind to the IL-4Rα chain. Because this receptor chain is also a component of the receptor for a related cytokine, Interleukin-13 (IL-13), dupilumab blocks the signals from both cytokines. This dual-action blockade has proven effective in treating moderate-to-severe atopic dermatitis and certain types of asthma.