Interleukin-36 beta (IL-36β) (IL-36β)

Interleukin-36 beta (IL-36β), encoded by the IL1F8 gene, is a pro-inflammatory cytokine belonging to the Interleukin-1 (IL-1) family (Source: UniProt Q9NZH7). It is primarily expressed in keratinocytes and various immune cells, where it acts as a key mediator of the innate immune response. IL-36β is synthesized as an inactive precursor that requires proteolytic cleavage, typically by neutrophil-derived proteases like cathepsin G, to achieve full biological activity (Source: PubMed PMID: 21641392). Upon activation, it binds to the IL-36 receptor (IL-36R) and recruits the IL-1 receptor accessory protein (IL-1RAcP), triggering intracellular signaling through the NF-κB and MAPK pathways (Source: NCBI Gene ID: 27177). This signaling cascade induces the production of various chemokines and cytokines, amplifying the inflammatory environment. Clinically, dysregulation of IL-36β is a central driver in the pathogenesis of generalized pustular psoriasis (GPP) and is also implicated in plaque psoriasis and other inflammatory conditions (Source: PubMed PMID: 30551030). Therapeutic intervention currently focuses on blocking the IL-36 receptor to neutralize the activity of IL-36β and its related isoforms. Spesolimab, an FDA-approved monoclonal antibody targeting IL-36R, has demonstrated significant efficacy in treating GPP flares by interrupting this inflammatory loop (Source: FDA.gov).

Other names

IL1F8Interleukin-1 family member 8FIL1-etaIL-1 etaInterleukin-1 homolog 2

Blockade of the IL-36 receptor (IL-36R) to inhibit the pro-inflammatory signaling of IL-36 beta and other IL-36 isoforms (Source: PubMed PMID: 31039471).