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Hypertonic solution-induced preconditioning reduces inflammation and mortality rate.

Rosangela Nascimento Pimentel1, Ricardo Costa Petroni1, Hermes Vieira Barbeiro1

  • 11Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.

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Hypertonic saline (HS) preconditioning in mice reduced mortality and systemic inflammation following a lethal lipopolysaccharide (LPS) challenge. This suggests HS can reprogram the inflammatory response, offering a protective effect.

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Hypertonic solutionInflammationPreconditioningSepsisTolerance

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Area of Science:

  • Critical care medicine
  • Immunology
  • Pharmacology

Background:

  • Dysregulated inflammation causes organ damage in critical care patients.
  • Preconditioning/tolerance strategies aim to prevent exacerbated inflammatory responses.
  • Hypertonic saline (HS) is investigated as a potential preconditioning agent.

Purpose of the Study:

  • To analyze 7.5% hypertonic saline (HS) as an inducer of preconditioning.
  • To evaluate HS protection against a lethal dose of lipopolysaccharide (LPS) in mice.
  • To assess the modulation of the systemic inflammatory profile by HS.

Main Methods:

  • Male Balb/C mice received daily intravenous injections of HS (7.5% NaCl) for 3 days.
  • On day 8, mice were challenged with a lethal dose of LPS (15 mg/kg).
  • Macrophage mRNA expression was analyzed via microarray to identify HS-activated pathways.

Main Results:

  • HS preconditioning significantly reduced mortality after LPS challenge.
  • HS treatment decreased the release of plasma cytokines in LPS-challenged mice.
  • Microarray analysis revealed HS increased expression of Mapkbp1 and Atf3 genes.

Conclusions:

  • Hypertonic saline (HS) effectively induces a preconditioning/tolerance state.
  • HS reduces mortality and mitigates the inflammatory response following LPS challenge.
  • HS preconditioning reprograms the inflammatory response, leading to reduced cytokine production.