interleukin1receptorer

Interleukin-1 receptor (IL-1R) refers to a family of cell-surface receptors that bind the pro-inflammatory cytokines interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β). The best characterized member is IL-1 receptor type I (IL-1R1), which initiates signaling leading to inflammatory gene expression. A second member, IL-1 receptor type II (IL-1RII), acts primarily as a decoy receptor that binds IL-1 but lacks a signaling domain, thereby dampening IL-1 activity. The IL-1 receptor accessory protein (IL-1RAcP) is a coreceptor required to form an active signaling complex with IL-1R1. Other IL-1 receptor family members, such as IL-1 receptor–related proteins, participate in specialized or regulatory roles in the immune and nervous systems.

Signaling occurs when IL-1 binds IL-1R1, and IL-1RAcP is recruited to form a receptor complex. The Toll/IL-1 receptor (TIR) domains recruit adaptor molecules such as MyD88, which in turn activate IRAK kinases and TRAF6, leading to activation of NF-κB and MAP kinases. This results in transcription of pro-inflammatory genes, chemokines, and cytokines. IL-1RII lacks the intracellular TIR domain and therefore does not signal; it reduces IL-1 availability by sequestering the ligand. Soluble forms of IL-1RII or IL-1RAcP can modulate signaling in the extracellular space.

Physiological and clinical significance: IL-1 signaling drives fever, leukocyte recruitment, and acute-phase responses. It is implicated in autoinflammatory diseases such as cryopyrin-associated periodic syndromes and rheumatoid arthritis. Therapeutic strategies include IL-1 blockade: anakinra, a recombinant IL-1 receptor antagonist; canakinumab, a monoclonal antibody against IL-1β; and rilonacept, a fusion protein that traps IL-1β and IL-1α.

Regulation and research: Expression of IL-1 receptors is regulated by cell type and inflammation. Genetic variations in IL1R genes influence susceptibility to inflammatory diseases. Ongoing research explores roles in metabolic disorders, neuroinflammation, and cancer.