Prevention of autoimmune diabetes by FTY720 in nonobese diabetic mice

Transplantation. 2002 Dec 27;74(12):1684-6. doi: 10.1097/00007890-200212270-00006.

Abstract

Background: FTY720 prevents allograft rejection with remarkable potency without inducing generalized immunosuppression. We determined the effect of FTY720 on development of autoimmune diabetes in nonobese diabetic (NOD) mice.

Methods: NOD mice were given FTY720 (0.5 mg/kg, orally) five times per week starting from 4 weeks of age.

Results: Daily FTY720 prevented development of diabetes in 15 of 16 treated mice, whereas 70% of untreated NOD mice became diabetic by 35 weeks of age. Withdrawal of FTY720 at 35 weeks of age led to development of diabetes within 2 weeks in five mice, whereas the remaining mice maintained diabetes-free conditions for up to 44 weeks of age. No side effect of the drug was seen throughout the treatment period. FTY720 also prevented cyclophosphamide-induced diabetes in NOD mice.

Conclusions: FTY720 is a safe and benign therapeutic agent that may be used chronically in prediabetic individuals.

MeSH terms

  • Animals
  • Body Weight
  • Cyclophosphamide
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Fingolimod Hydrochloride
  • Graft Rejection / drug therapy
  • Immunosuppressive Agents / pharmacology*
  • Islets of Langerhans Transplantation*
  • Mice
  • Mice, Inbred NOD
  • Propylene Glycols / pharmacology*
  • Sphingosine / analogs & derivatives

Substances

  • Immunosuppressive Agents
  • Propylene Glycols
  • Cyclophosphamide
  • Fingolimod Hydrochloride
  • Sphingosine