Interleukin 23 (IL-23) is a cytokine, a small protein that acts as a messenger in the immune system. It helps activate the immune system when the body faces threats like bacteria or fungi, guiding immune cell responses.
The Role of Interleukin 23 in the Body
IL-23 regulates inflammatory responses. It is produced primarily by dendritic cells and macrophages. IL-23 maintains and expands T-helper 17 (Th17) cells, which produce pro-inflammatory cytokines important for fighting infections.
IL-23 also protects against extracellular fungi and bacteria. When an antigen is recognized, IL-23 secretion is stimulated. It helps gather immune cells to infection or injury sites to combat pathogens, supporting the body’s defense and tissue balance.
Interleukin 23 in Autoimmune and Inflammatory Conditions
Dysregulation or overactivity of IL-23 contributes to autoimmune and chronic inflammatory diseases. The body may overproduce IL-23 without infection, leading to increased inflammation. This overabundance can affect the skin, joints, and gut.
The IL-23/Th17 axis is a key mechanism: IL-23 stimulates Th17 cell differentiation and proliferation, leading to excessive pro-inflammatory cytokines. This sustained response damages tissues. In inflammatory bowel disease (IBD), the IL-23 pathway may remain active, causing chronic gut inflammation.
IL-23 plays a role in conditions such as psoriasis, a chronic skin condition characterized by red, scaly patches. It also contributes to psoriatic arthritis, which affects the joints, and Crohn’s disease, a type of IBD. Other conditions where IL-23 is implicated include ankylosing spondylitis, rheumatoid arthritis, and multiple sclerosis. The continuous activation of the IL-23/Th17 axis drives the chronic inflammation seen in these diseases. This makes IL-23 a target for therapeutic research.
Targeting Interleukin 23 for Treatment
Understanding IL-23’s role in disease has led to the development of targeted therapies known as IL-23 inhibitors or biologics. These medications work by specifically blocking the action of IL-23, which helps to reduce inflammation and manage symptoms in conditions driven by its overactivity. By targeting IL-23, these inhibitors reduce the activity of Th17 cells, mitigating the inflammatory response.
IL-23 inhibitors function by binding to a specific subunit of the IL-23 cytokine, preventing it from interacting with its receptor on immune cells. This blockade interrupts signaling pathways that lead to the activation and proliferation of Th17 cells and the production of inflammatory cytokines. This targeted approach aims to minimize side effects compared to broader immunosuppressive treatments, as it focuses on a specific pathway.
Common examples of IL-23 inhibitors include ustekinumab, risankizumab, guselkumab, and tildrakizumab. Ustekinumab targets the p40 subunit, which is shared by both IL-12 and IL-23. Newer agents like risankizumab, guselkumab, and tildrakizumab specifically target the p19 subunit, which is unique to IL-23. This specific targeting preserves other immune functions while reducing inflammation, leading to improvements in skin clearance and joint function in conditions like psoriasis and psoriatic arthritis.