Interleukin-1 alpha (IL-1α) and Interleukin-1 beta (IL-1β) (IL-1α and IL-1β)

Interleukin-1 alpha (IL-1α) and Interleukin-1 beta (IL-1β) are potent pro-inflammatory cytokines that play central roles in the innate immune response (UniProt P01583, P01584). While IL-1α is often membrane-bound and acts as an alarmin released upon cell death, IL-1β is secreted following inflammasome activation (Dinarello, 2011, Blood). Both ligands bind to the same cell surface receptor, Interleukin-1 receptor type 1 (IL-1R1), to trigger signaling pathways that lead to the production of other inflammatory mediators (Weber et al., 2010, Sci Signal). Dysregulation of these cytokines is implicated in various chronic inflammatory conditions, including hidradenitis suppurativa and osteoarthritis (Kloppenburg et al., 2019, Ann Rheum Dis). Lutikizumab (ABT-981) is a dual-variable-domain immunoglobulin (DVD-Ig) designed to neutralize both IL-1α and IL-1β simultaneously (Fleischmann et al., 2019, Ann Rheum Dis). By blocking both ligands, lutikizumab provides a more comprehensive blockade of the IL-1 pathway than agents targeting only one ligand, potentially addressing diseases where both isoforms contribute to the inflammatory milieu (AbbVie, 2024).

Other names

IL-1AIL-1BHematopoietin-1CatabolinIL-1 alphaIL-1 betaInterleukin-1 family ligands

Lutikizumab is a dual-variable-domain immunoglobulin (DVD-Ig) that binds to and neutralizes both IL-1α and IL-1β ligands, preventing them from interacting with the Interleukin-1 receptor type 1 (IL-1R1) and thereby inhibiting downstream pro-inflammatory signaling (Fleischmann et al., 2019, Ann Rheum Dis).