Lithium carbonate attenuates sepsis-induced acute lung injury by inhibiting the GSDMD/IL-1β pathway
Cai Qingli
Zhang Anqiang
Huang Hong
Yue Ying
Xiang Jing
Abstract：Objective To investigate the role of lithium carbonate(LC)in alleviating sepsis-induced acute lung injuries(ALI)by suppressing gasdermin D(GSDMD)-mediated pyroptosis.Methods In vitro experiments were first conducted to assess the effect of LC on interleukin-1β(IL-1β)levels in lipopolysaccharide(LPS)-stimu-lated monocytes.Subsequently,70 male C57BL/6 mice(20-25 g,6-8 weeks old)were randomly assigned to control group(n=10),sepsis group(LPS group,17 mg/kg LPS intraperitoneal injection,n=30),and sepsis+LC group(LPS+LC group,LPS+20 mg/kg LC via gavage,n=20).The 6-d survival outcomes of rates were recorded.Lung inflammatory cell infiltration was evaluated through HE staining and lung injury scoring.Serum levels of IL-1β,TNF-α,and IL-6 were measured by ELISA.Pulmonary pyroptosis and inflammation were assessed via qRT-PCR a-nalysis of IL-6,TNF-α,GSDMD,and CXCL15 mRNA expression.Results In vitro,LC significantly suppressed LPS-induced IL-1β secretion in monocytes(ng/mL,0.91±0.13 vs.1.35±0.11,P<0.001)in a concentration-dependent manner.In vivo,the LPS+LC group exhibited significantly higher 6-d survival than the LPS group(50.0%vs.23.3%,P=0.04).Reduced lung injury scores by HE stain(0.67±0.09 vs.0.51±0.06,P=0.04),de-creased pulmonary levels of TNF-α,IL-6,IL-1β,and CXCL15,and downregulated GSDMD expression were observed in the LPS+LC group(all P<0.05).Conclusion LC mitigates pyroptosis and inflammation in sepsis-induced ALI by inhibiting the GSDMD/IL-1β pathway,thereby improving survival.These findings support its potential as a therapeutic agent for sepsis-associated ALI.
Keywords：Lithium carbonateGasdermin DSepsis-induced acute lung injuriesPyroptosisInflammation
Publication Date：2026-01-15
Online Publishing Date：2026-03-03(First online date of this platform, not the publication date of the document)
Pages：6( 61-66 )