Hypertonic solution-induced preconditioning reduces inflammation and mortality rate

J Inflamm (Lond). 2019 Jul 3;16:16. doi: 10.1186/s12950-019-0220-4. eCollection 2019.

Abstract

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.

Keywords: Hypertonic solution; Inflammation; Preconditioning; Sepsis; Tolerance.