Interleukin-13, commonly known as IL-13, is a signaling protein within the immune system. It functions as a chemical messenger, facilitating communication between different immune cells. This cytokine helps to coordinate diverse immune responses throughout the body.
The Primary Role of IL-13 in the Immune System
Interleukin-13 plays a central role in orchestrating Type 2 immune responses, a specialized branch of the body’s defense system [2_search_1, 3_search_1, 4_search_1, 5_search_1]. IL-13 helps direct various cellular activities in these responses. Primary producers of IL-13 include T helper 2 (Th2) cells and innate lymphoid cells (ILC2s) [2_search_1, 2_search_2, 3_search_1, 4_search_2, 5_search_2]. Other immune cells like mast cells, basophils, and eosinophils also contribute to its release [2_search_2].
IL-13 is important for host protection against parasitic infections, such as helminths [1_search_1, 3_search_1, 4_search_1, 1_search_4, 2_search_4, 3_search_4, 4_search_4, 5_search_4]. It induces specific changes in the gut environment to facilitate parasite expulsion [1_search_3, 2_search_4]. These changes include enhanced intestinal muscle contractions and increased glycoprotein secretion from gut epithelial cells, which helps dislodge and remove the organisms [1_search_3, 2_search_4]. Beyond parasite defense, IL-13 also contributes to the broader regulation of inflammation and the production of antibodies, supporting a balanced immune system function [1_search_1, 3_search_1, 4_search_1, 5_search_1].
Connection to Allergic and Inflammatory Conditions
While Type 2 immune responses are protective against parasites, they can become overactive or misdirected, leading to allergic and inflammatory conditions [1_search_5, 3_search_5, 4_search_5]. IL-13’s actions contribute to the symptoms observed in these diseases. In asthma, IL-13 is a significant contributor to airway inflammation and hyperresponsiveness [1_search_5, 2_search_5, 1_search_6, 2_search_6, 3_search_6]. It promotes the overproduction of mucus within the airways [1_search_5, 2_search_5, 1_search_6]. Levels of IL-13 are often elevated in the sputum and bronchial tissues of individuals with asthma [1_search_6].
In atopic dermatitis, also known as eczema, IL-13 disrupts the skin’s barrier function [1_search_7, 2_search_7, 3_search_7, 5_search_7]. It reduces the expression of proteins like filaggrin, loricrin, involucrin, and desmoglein, which are important for maintaining skin integrity [1_search_7, 2_search_7, 3_search_7, 5_search_7]. This disruption allows allergens and irritants to penetrate the skin more easily, driving inflammation and intense itching [1_search_7, 2_search_7, 5_search_7]. IL-13 also contributes to a cycle involving skin microbiome imbalances, promoting the adhesion of bacteria such as Staphylococcus aureus [3_search_3, 5_search_7].
Allergic rhinitis, commonly known as hay fever, also involves IL-13, which along with IL-4, activates B cells to produce immunoglobulin E (IgE), an antibody linked to allergic reactions [3_search_5]. This cytokine also induces goblet cell hyperplasia and mucus hypersecretion in the nasal passages, leading to characteristic symptoms [3_search_5]. Elevated serum levels of IL-13 are observed in patients with allergic rhinitis [3_search_5].
Eosinophilic esophagitis (EoE), an allergic condition affecting the esophagus, involves IL-13 [1_search_8, 3_search_8, 5_search_8]. In EoE, IL-13 contributes to allergen-driven inflammation and increased Type 2 cytokines [1_search_8, 3_search_8, 5_search_8]. It specifically induces higher levels of eotaxin, a chemical signal that attracts eosinophils to the esophagus [1_search_8, 2_search_8]. This cytokine can also contribute to the structural changes and remodeling seen in esophageal tissue [2_search_8].
Influence on Tissue Changes and Fibrosis
Chronic exposure to elevated IL-13 levels can lead to long-term structural changes in various tissues, a process known as tissue remodeling [1_search_5, 2_search_5, 3_search_1, 2_search_10, 3_search_10, 4_search_10, 5_search_5_search_10]. This cytokine drives these alterations, affecting tissue architecture. IL-13 stimulates goblet cells, particularly in the airways and gut, to produce excessive mucus, a process known as mucus hypersecretion [1_search_5, 2_search_5, 1_search_9, 2_search_9, 3_search_9, 4_search_9, 5_search_9]. This overproduction is a characteristic feature of conditions like asthma and eosinophilic esophagitis, contributing to airway obstruction and impaired mucociliary clearance [1_search_5, 2_search_5, 2_search_9, 2_search_10, 3_search_9].
IL-13 also promotes fibrosis, a process involving excessive collagen accumulation and other extracellular matrix proteins [1_search_10, 2_search_10, 3_search_10, 4_search_10, 5_search_10]. This leads to tissue hardening and scarring. IL-13 activates fibroblasts and induces the expression of type I collagen [2_search_10]. It can work in conjunction with other signaling molecules, such as transforming growth factor beta 1 (TGF-β1), to sustain collagen accumulation and increase tissue stiffness [5_search_10, 1_search_11]. These persistent changes contribute to the chronic and progressive nature of some allergic and inflammatory diseases.
Medical Treatments Targeting IL-13
Medical treatments for conditions driven by excessive IL-13 activity often involve blocking its effects. Monoclonal antibodies are a therapeutic strategy designed to specifically target and neutralize biological molecules [1_search_12, 2_search_12, 3_search_12, 4_search_12]. These drugs work by binding to either IL-13 itself or its receptor, preventing the cytokine from sending its signals and thereby interrupting downstream inflammatory pathways [3_search_12, 4_search_12, 5_search_12]. This approach can reduce the activation of signaling molecules like STAT6, involved in gene expression related to inflammation and tissue changes [3_search_12].
Tralokinumab is a fully human IgG4λ monoclonal antibody that specifically binds to IL-13 [4_search_13]. It prevents IL-13 from interacting with its receptor chains, including IL-13Rα1 and IL-13Rα2 [3_search_13, 4_search_13, 5_search_13]. This drug is approved for treating moderate-to-severe atopic dermatitis, where it helps improve skin barrier function by restoring levels of proteins like filaggrin [1_search_13, 2_search_13, 3_search_13, 4_search_13].
Lebrikizumab is an IgG4 monoclonal antibody that targets IL-13 [1_search_14, 2_search_14]. It works by selectively inhibiting IL-13 signaling through a specific receptor complex known as the IL-4Rα/IL-13Rα1 heterodimer [1_search_14, 3_search_14, 4_search_14, 5_search_14]. Unlike some other treatments, lebrikizumab does not prevent IL-13 from binding to the IL-13Rα2 “decoy” receptor, potentially allowing this natural regulatory mechanism to remain active [1_search_14, 5_search_14]. This medication is approved for treating moderate-to-severe atopic dermatitis [1_search_14].
Dupilumab represents a different approach by targeting the IL-4 receptor alpha (IL-4Rα) subunit [1_search_15, 2_search_15, 5_search_15]. This receptor subunit is shared by both IL-4 and IL-13 receptor complexes [1_search_15, 2_search_15, 3_search_15, 4_search_15, 5_search_15]. By binding to IL-4Rα, dupilumab effectively blocks the signaling of both IL-4 and IL-13, addressing a broader range of Type 2 inflammatory pathways [1_search_15, 2_search_15, 3_search_15, 4_search_15, 5_search_15]. Dupilumab is approved for several conditions, including atopic dermatitis and asthma [1_search_15, 3_search_15, 4_search_15, 5_search_15].