Interleukin-1 receptor type 1 (IL-1RI)

The interleukin-1 beta signaling pathway is initiated by the binding of the pro-inflammatory cytokine interleukin-1 beta (IL-1β) to its main receptor, interleukin-1 receptor type 1 (IL-1RI), on the cell surface. This triggers the recruitment of accessory proteins (such as IL-1 receptor accessory protein, IL-1RAcP) and the activation of intracellular signal transduction cascades, most notably the NF-κB and MAP kinase pathways, leading to transcription of inflammatory genes. The pathway is pivotal in coordinating innate and adaptive immune responses, pyroptosis, fever, and stress responses. Pathological dysregulation of this pathway is implicated in a variety of autoinflammatory and autoimmune disorders, cancer progression, and chronic inflammatory diseases. Therapeutic targeting usually focuses on blocking IL-1β itself or its receptor IL-1RI to inhibit downstream inflammatory responses.

Other names

IL-1R1CD121aIL1Rinterleukin-1 beta receptorinterleukin-1 type I receptor

Drugs targeting this pathway primarily act through competitive antagonism of the IL-1RI receptor (e.g., Anakinra binds IL-1RI and blocks IL-1β binding), neutralization of the IL-1β ligand (e.g., Canakinumab directly binds and neutralizes IL-1β), or acting as a ligand trap (e.g., Rilonacept binds circulating IL-1β and prevents receptor activation).