Age- and sex-dependent heterogeneity during LPS-induced murine acute lung injury

Acute respiratory distress syndrome (ARDS) remains difficult to treat due to its heterogeneous etiology. In this study, a mouse model of intratracheal lipopolysaccharide (LPS) instillation was used to investigate age- and sex-dependent immune responses. After six hours of LPS exposure and one hour of mechanical ventilation, immune cell subtypes as well as mRNA and protein expression were analyzed. Aged mice exhibited a basal pro-inflammatory immune signature already under sham conditions, whereas young mice displayed a more balanced response with parallel pro- and anti-inflammatory mechanisms. Notably, aged female LPS treated mice exhibited an exclusively pro-inflammatory response. UMAP analysis revealed distinct clustering according to age, sex, and treatment, while aged male mice formed isolated clusters. These findings highlight the importance of considering age- and sex-specific therapeutic strategies for ARDS treatment.