Avitinib suppresses NLRP3 inflammasome activation and ameliorates septic shock in mice
SHANG Feifei
SHI Xiaoke
ZENG Yao
TAO Xunqian
LI Tianzhen
LIANG Yan
YANG Yanqin
SONG Chuanwang
Abstract：Objective To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism.Methods Mouse bone marrow-derived macrophages(BMDM),human monocytic leukemia cell line THP-1,and peripheral blood mononuclear cells(PBMC)isolated from healthy volunteers were pre-treated with avitinib,followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin,monosodium urate(MSU)crystals,or adenosine triphosphate(ATP).Non-canonical NLRP3 inflammasome activation was induced via intracellular transfection of lipopolysaccharide(LPS).Western blotting was used to detect the secretory protein markers of NLRP3 inflammasome activation and assess pyroptosis,and the levels of inflammatory cytokines in cell culture supernatant were determined with ELISA.In a mouse model of LPS-induced septic shock,the effect of avitinib treatment on the levels of inflammatory cytokines in serum and peritoneal lavage fluid were examined with ELISA,and survival curves of the mice were plotted using the Kaplan-Meier method.Results Avitinib significantly inhibited NLRP3 inflammasome activation in multiple cell types,and dose-dependently reduced IL-1β secretion and caspase-1 cleavage while suppressing GSDMD-mediated pyroptosis without obviously affecting IL-6 or TNF-α levels.In the mouse models of LPS-induced septic shock,avitinib significantly lowered IL-1β levels in serum and peritoneal fluid and extended survival time of the mice.Conclusion Avitinib suppresses NLRP3 inflammasome activation and alleviates septic shock in mice.
Keywords：avitinibNLRP3 inflammasomeEGFR inhibitorseptic shock
Publication Date：2025-08-20
Online Publishing Date：2025-09-15(First online date of this platform, not the publication date of the document)
Pages：9( 1697-1705 )