IL18 - Interleukin 18| Elisa - Clia - Antibody - Protein

Background

Interleukin-18 (IL-18) is a pro-inflammatory cytokine that belongs to the interleukin-1 (IL-1) family. It was originally identified as an interferon-gamma (IFN-γ) inducing factor and plays a crucial role in both innate and adaptive immunity. IL-18 is produced by a variety of cells, including macrophages, dendritic cells, epithelial cells, and Kupffer cells in the liver. It is synthesized as an inactive precursor (pro-IL-18) and requires cleavage by caspase-1 within the inflammasome complex to become active. IL-18 is involved in promoting Th1 and Th2 responses, enhancing the production of IFN-γ, and stimulating the activity of natural killer (NK) cells and T cells.

Protein Structure

IL-18 is synthesized as a 24 kDa precursor protein and is processed into its mature form:

• Pro-IL-18 (24 kDa): The inactive precursor form that is produced in response to inflammatory signals.
• Mature IL-18 (18 kDa): The active form generated by caspase-1-mediated cleavage. This mature cytokine is then secreted and binds to its receptor to exert biological effects.

IL-18 functions by binding to the IL-18 receptor (IL-18R), which consists of two subunits: IL-18Rα and IL-18Rβ. Upon binding to its receptor, IL-18 activates downstream signaling pathways, including NF-κB and MAPKs, leading to the production of inflammatory mediators.

Classification and Subtypes

IL-18 is a member of the IL-1 cytokine family, which includes other cytokines such as IL-1α, IL-1β, IL-33, and IL-36. IL-18 is unique within this family due to its role in inducing IFN-γ production and its involvement in both Th1 and Th2 immune responses.

Function and Biological Significance

IL-18 has several critical functions in the immune system:

• Induction of IFN-γ: IL-18 is a potent inducer of IFN-γ production from T cells and NK cells, which is essential for the activation of macrophages and the promotion of Th1 responses.
• Enhancement of NK Cell Activity: IL-18 enhances the cytotoxic activity of NK cells, contributing to the body's defense against viral infections and tumors.
• Promotion of Th1 and Th2 Responses: IL-18 plays a role in the differentiation and function of both Th1 and Th2 cells, making it a versatile cytokine in adaptive immunity.
• Synergy with Other Cytokines: IL-18 often works in synergy with IL-12 and IL-15 to enhance immune responses, particularly in the production of IFN-γ and the activation of NK cells.

Clinical Issues

Dysregulation of IL-18 is associated with various pathological conditions:

• Chronic Inflammatory Diseases: Elevated levels of IL-18 are linked to autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease (IBD), and psoriasis.
• Infectious Diseases: IL-18 plays a role in the immune response to infections, and its dysregulation can contribute to both hyperinflammatory responses and insufficient immune activation.
• Cancer: IL-18 can have dual roles in cancer, either promoting anti-tumor immunity through IFN-γ production or contributing to tumor progression through chronic inflammation.
• Metabolic Disorders: IL-18 has been implicated in the pathogenesis of metabolic disorders such as obesity and type 2 diabetes, where it can influence insulin sensitivity and inflammatory responses.

Summary

Interleukin-18 (IL-18) is a key cytokine in the regulation of immune responses, bridging innate and adaptive immunity. It is produced as an inactive precursor and activated by caspase-1 cleavage. IL-18 induces IFN-γ production, enhances NK cell activity, and promotes both Th1 and Th2 responses. Dysregulation of IL-18 is linked to chronic inflammatory diseases, infections, cancer, and metabolic disorders. Understanding IL-18's mechanisms and roles in disease provides insights into potential therapeutic targets for various inflammatory and immune-related conditions.