Hypertonic saline reduces neutrophil-epithelial interactions in vitro and gut tissue damage in a mouse model of

Wolfgang Tillinger1, Declan F McCole, Stephen J Keely

  • 1Division of Gastroenterology, Department of Medicine, University of California, San Diego, Mailcode 0063, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Insights

Hypertonic saline (HS) inhibits polymorphonuclear neutrophil (PMN) migration across intestinal cells and reduces gut tissue damage in experimental colitis. This suggests HS may be valuable for treating PMN-mediated intestinal inflammation.

Area of Science:

  • Gastroenterology
  • Immunology
  • Pharmacology

Background:

  • Transepithelial migration of polymorphonuclear neutrophils (PMN) is critical in intestinal inflammatory diseases like inflammatory bowel disease.
  • Hypertonic saline (HS) is known to inhibit various PMN functions.

Purpose of the Study:

  • To investigate the hypothesis that HS can inhibit PMN transepithelial migration and prevent inflammatory events in experimental colitis.
  • To evaluate the therapeutic potential of HS in managing colitis.

Main Methods:

  • In vitro: Human PMN were treated with HS and their transmigration across T84 epithelial cell monolayers was assessed.
  • In vitro: Monolayer disruption was measured by transepithelial conductance changes in an Ussing chamber.
  • In vivo: Colitis was induced in mice using dextran sulfate sodium (DSS) and animals were treated with HS or normal saline (NS).
  • In vivo: Inflammation severity was evaluated using disease activity index and histology scores.

Main Results:

  • HS significantly reduced PMN migration and T84 monolayer disruption in vitro, demonstrating a dose-dependent effect.
  • In vivo, HS treatment attenuated DSS-induced colitis, leading to improved histology scores compared to NS and DSS control groups.
  • HS effectively inhibited PMN transmigration and reduced gut tissue damage in experimental models.

Conclusions:

  • Hypertonic saline inhibits PMN transepithelial migration in vitro and reduces gut tissue damage in a mouse model of colitis.
  • HS demonstrates potential clinical value in mitigating PMN-mediated intestinal damage and inflammation.

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