Interleukin-1 receptor signaling complex (IL-1R complex)

The Interleukin-1 (IL-1) receptor signaling complex is a pivotal assembly in the innate immune system, responsible for mediating inflammatory responses [UniProt P14778]. The complex is primarily composed of the Interleukin-1 receptor type 1 (IL-1R1) and the Interleukin-1 receptor accessory protein (IL-1RAcP), which form a heterodimer upon binding of the pro-inflammatory cytokines IL-1 alpha or IL-1 beta [Nature Immunology, 2010]. This assembly brings together the intracellular Toll-Interleukin-1 Receptor (TIR) domains, initiating a signaling cascade that recruits MyD88 and Interleukin-1 receptor-associated kinases (IRAKs) [Science Signaling, 2010]. The resulting activation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways leads to the transcription of numerous pro-inflammatory genes, including other cytokines, chemokines, and adhesion molecules [PubMed, 2011]. Dysregulation or overactivation of this signaling complex is implicated in a wide range of diseases, such as rheumatoid arthritis, gout, and rare autoinflammatory conditions like cryopyrin-associated periodic syndromes (CAPS) [Blood, 2011]. Pharmacological intervention typically involves blocking the receptor with antagonists like Anakinra or neutralizing the ligands with monoclonal antibodies such as Canakinumab or decoy receptors like Rilonacept [DrugBank]. While highly effective in controlling systemic inflammation, inhibition of this complex can increase patient susceptibility to serious infections and may lead to transient neutropenia [NIH, 2023].

Other names

IL-1R1/IL-1RAcP complexInterleukin-1 receptor type 1 complexIL-1 receptor complexIL-1 signaling assemblyIL-1R1/IL-1RAP complex

Competitive inhibition of IL-1R1 by recombinant IL-1 receptor antagonist (Anakinra) or ligand sequestration (Canakinumab, Rilonacept) to prevent the formation of the active signaling complex [StatPearls, 2023].