Background Dysregulated inflammatory response is common cause of organ damage in critical care patients. Preconditioning/tolerance is a strategy to prevent exacerbated inflammation. The aim of this study is to analyze hypertonic saline 7.5% as a potential inducer of preconditioning that protect from a lethal dose of LPS and modulates systemic inflammatory profile in mice. Methods Male Balb/C mice received intravenous (i.v.) injections of Hypertonic solution (NaCl 7.5%) (0.8 ml) for 3 days, on day 8th was challenged with LPS 15 mg/kg. Controls with Saline 0.9%, urea and sorbitol were performed. Microarray of mRNA expression was analyzed from HS versus saline from macrophages to identified the pathways activated by HS. Results HS preconditioning reduced mortality after LPS injection as well reduced the cytokines release in plasma of the animals challenged by LPS. In order to check how HS induces a preconditioning state we measured plasma cytokines after each HS infusion. Repeated HS injections induced a state of preconditioning that reprograms the inflammatory response, resulting in reduced inflammatory cytokine production. A microarray of mRNA demonstrated that Hypertonic solution increased the expression of several genes in special Mapkbp1 and Atf3. Conclusion hypertonic solution induces preconditioning/tolerance reducing mortality and inflammatory response after LPS challenge.

中文翻译：

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高渗溶液诱导的预处理可降低炎症和死亡率。

背景 失调的炎症反应是重症监护患者器官损伤的常见原因。预处理/耐受是一种预防炎症加剧的策略。本研究的目的是分析 7.5% 的高渗盐水作为预处理的潜在诱导剂，该诱导剂可防止致命剂量的 LPS 并调节小鼠的全身炎症特征。方法 雄性 Balb/C 小鼠接受静脉注射 (iv) 高渗溶液 (NaCl 7.5%) (0.8 ml) 3 天，第 8 天用 LPS 15 mg/kg 攻击。用 0.9% 的盐水、尿素和山梨糖醇进行对照。分析来自 HS 的 mRNA 表达微阵列与来自巨噬细胞的盐水，以确定由 HS 激活的途径。结果 HS 预处理降低了 LPS 注射后的死亡率，也降低了 LPS 攻击动物血浆中细胞因子的释放。为了检查 HS 如何诱导预处理状态，我们在每次 HS 输注后测量血浆细胞因子。重复注射 HS 会诱导一种重新编程炎症反应的预处理状态，从而导致炎症细胞因子的产生减少。mRNA 微阵列表明，高渗溶液增加了特殊 Mapkbp1 和 Atf3 中几个基因的表达。结论高渗溶液诱导预处理/耐受，降低 LPS 攻击后的死亡率和炎症反应。重复注射 HS 会诱导一种重新编程炎症反应的预处理状态，从而导致炎症细胞因子的产生减少。mRNA 微阵列表明，高渗溶液增加了特殊 Mapkbp1 和 Atf3 中几个基因的表达。结论高渗溶液诱导预处理/耐受，降低 LPS 攻击后的死亡率和炎症反应。重复注射 HS 会诱导一种重新编程炎症反应的预处理状态，从而导致炎症细胞因子的产生减少。mRNA 微阵列表明，高渗溶液增加了特殊 Mapkbp1 和 Atf3 中几个基因的表达。结论高渗溶液诱导预处理/耐受，降低 LPS 攻击后的死亡率和炎症反应。