Recovery from an acute systemic and central LPS-inflammation challenge is affected by mouse sex and genetic background

Genetic and sexual factors influence the prevalence and the pathogenesis of many inflammatory disorders. In this study their relevance on the peripheral and central inflammatory status induced by a peripheral injection of lipopolysaccharide (LPS) was evaluated. BALB/c and CD-1 male and female mice were intraperitoneally injected with LPS. Spleens and brains were collected 2 and 72 hours later to study the levels of IL-6, TNF-α and IL-1β. Percentage of microglia and astrocytes was determined in the cortex and hippocampus. Locomotor activity was registered before and during the 72 hours after LPS-treatment. Two hours after LPS-injection, a peripheral increase of the three cytokines was found. In brains, LPS increased TNF-α only in males with higher levels in CD-1 than BALB/c. IL-1β increased only in CD-1 males. IL-6 increased in both strains with lower levels in BALB/c females. Peripheral and central levels of cytokines decline 72 hrs after LPS-treatment whilst a significantly increase of Iba-1 expression was detected. A dramatic drop of the locomotor activity was observed immediately after LPS injection. Our results show that acute systemic administration of LPS leads to peripheral and central increase of pro-inflammatory cytokines and microglia activation, in a strain and sex dependent manner.遗传与性别因素可影响多种炎症性疾病的患病率与发病机制。本研究评估了遗传与性别因素在脂多糖（lipopolysaccharide, LPS）外周注射诱导的外周及中枢炎症状态中的关联作用。实验对BALB/c与CD-1品系的雌雄小鼠进行脂多糖腹腔注射造模，分别于注射后2小时与72小时采集脾脏与脑组织，检测IL-6、TNF-α及IL-1β的表达水平；同时检测大脑皮层与海马体中小胶质细胞及星形胶质细胞的占比，并于脂多糖处理前及处理后72小时内记录小鼠的自主活动能力。脂多糖注射后2小时，外周血中三种细胞因子的水平均显著升高。脑组织层面，脂多糖仅在雄性小鼠中升高TNF-α的表达，且CD-1品系小鼠的TNF-α水平高于BALB/c品系；IL-1β的表达仅在CD-1品系雄性小鼠中升高；IL-6的水平在两种品系小鼠中均有所升高，其中BALB/c雌性小鼠的IL-6水平更低。脂多糖处理后72小时，外周与中枢的细胞因子水平均出现下降，但Iba-1的表达量显著升高。小鼠的自主活动能力于脂多糖注射后即刻出现显著下降。本研究结果表明，脂多糖的急性全身给药可诱导外周与中枢促炎细胞因子水平升高及小胶质细胞活化，且该效应呈现品系与性别依赖性。