Question

Describe IL-18 biology and its role in inflammatory diseases.

Hint:

IL-18 is a potent cytokine that plays a critical role in inflammation, particularly in autoimmune diseases by promoting the activation of immune cells and the production of pro-inflammatory cytokines.

Answer 1

Step 1: Overview of IL-18 Biology.
IL-18, also known as interferon-gamma-inducing factor (IGIF), is a pro-inflammatory cytokine that plays a crucial role in the innate and adaptive immune responses. It is a member of the IL-1 cytokine family and is produced as an inactive precursor (pro-IL-18), which is cleaved by caspase-1 to become active. IL-18 primarily functions to induce the production of interferon-gamma (IFN-γ) from T cells and natural killer (NK) cells, promoting inflammation.
Step 2: Mechanism of Action.
IL-18 exerts its effects by binding to its receptor IL-18R on the surface of immune cells, particularly T cells and macrophages. This binding activates various intracellular signaling pathways, including NF-κB and MAPK, leading to the production of pro-inflammatory cytokines, such as TNF-α, IL-1, and IL-6, as well as IFN-γ. This cytokine cascade plays a central role in the inflammatory response.
Step 3: IL-18 in Inflammatory Diseases.
IL-18 has been implicated in several chronic inflammatory diseases, including rheumatoid arthritis (R, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and atherosclerosis. In these conditions, IL-18 contributes to sustained inflammation and tissue damage, often exacerbating disease progression.