The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice

Oncol Rep. 2006 Oct;16(4):699-703.

Abstract

To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the development of dextran sulfate sodium (DSS)-induced colitis and CD4+CD62L+ T cell transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to induce colitis. The CD4+CD62L+ T cell transfer colitis was induced by an intraperitoneal injection of CD4+CD62L+ spleen T cells into recipient CB17 SCID mice. The FTY720 was administered by lavage at a dose of 0.3 mg/kg/day. FTY720 was effective in preventing the body weight loss in the DSS-colitis model and the CD4+CD62L+ T cell transfer model. The disease activity index, histological colitis score, and MPO activity were all significantly lower in FTY720-treated mice than in the non-treated mice. Microscopically, mucosal edema, cellular infiltration and epithelial disruption were much more moderate in the FTY720-treated mice than in the non-treated mice. In both colitis models, FTY720 prevented the infiltration of CD4+ T cells into the inflamed colonic lamina propria. In conclusion, the development of DSS-colitis and CD4+CD62L+ T cell transfer colitis were significantly attenuated by FTY720. Since FTY720 is an immunosuppressive product that does not modulate T cell functions, it could be useful in the treatment of IBD patients.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Transplantation
  • Colitis / prevention & control*
  • Disease Models, Animal
  • Fingolimod Hydrochloride
  • Immunosuppressive Agents / pharmacology*
  • Inflammatory Bowel Diseases / prevention & control
  • Inflammatory Bowel Diseases / therapy
  • L-Selectin / biosynthesis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Propylene Glycols / pharmacology*
  • Receptors, Lysosphingolipid / metabolism
  • Receptors, Lysosphingolipid / physiology*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Spleen / metabolism

Substances

  • Immunosuppressive Agents
  • Propylene Glycols
  • Receptors, Lysosphingolipid
  • L-Selectin
  • Fingolimod Hydrochloride
  • Sphingosine