724 Evaluation of an anti-human IL-1β antibody in monosodium urate crystals-induced peritonitis model in hIL-1β HuGEMM™ mice

Background Gout is a chronic inflammatory disease featuring the deposition of monosodium urate (MSU) crystals in synovial fluid patients, followed by NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome activation bioactive IL-1β release, which recruits neutrophils to local inflammation sites. Blocking function becoming potent therapeutic approach for gout gouty arthritis. Conventional MSU-induced peritonitis C57BL/6 mice provides simple rapid evaluation therapeutics targeting activation. However, this murine model has limitations when it comes human-specific antibodies, example, anti-human (anti-hIL-1β) monoclonal antibodies (mAb). Thus, assess efficacy anti-hIL-1β mAb needed. We have developed hIL-1β knock-in mouse (hIL-1β HuGEMM™), able facilitate pre-clinical drugs specific human biological molecules especially ortholog not available. Therefore, an MSU induced using HuGEMM™ robust evaluate therapies hIL-1β. Methods were injected intraperitoneally into (hIL-1β) mice, where coding sequence was replaced Prior crystal administration, received treatment either vehicle or antibody. Six hours post injection, serum lavage flushed with PBS collected. Subsequently, cytokine levels determined MSD, population polymorphonuclear leukocytes (PMNs) (live CD11b+ Ly-6GHi cells) analysed flow cytometry. Results The group showed dramatic increase secretion PMN leukocytes, comparison that did receive MSU, suggests successful induction acute response peritoneal cavity. In contrast, single administration antibody 24 prior injection exhibited significantly lower level compared group, implies efficaciously neutralized secretion. addition, TNF-α IL-6, two further cytokines downstream IL-1β, reduced group. leukocyte infiltration change Conclusions study, crystals-induced successfully established HuGEMM potential immune blockades.