Journal
CLINICAL IMMUNOLOGY
Volume 107, Issue 1, Pages 30-35Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S1521-6616(02)00054-2
Keywords
FTY720; autoimmune diabetes; NOD mice; insulitis; lymphocytes
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Funding
- NICHD NIH HHS [U54 HD 28934] Funding Source: Medline
- NIDDK NIH HHS [DK 062610, P30 DK 063609-01] Funding Source: Medline
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FrY720 is a novel immune regulatory drug derived from the fungal sphingosine analog ISP-1 (myriocin). FTY720 causes a redistribution of lymphocytes from circulation to secondary lymphoid tissues. Type I diabetes is an autoimmune disorder caused by cellular-mediated destruction of insulin-producing pancreatic 0 cells in the islets of Langerhans. Indeed, local infiltration of islets by mononuclear cells is the hallmark of Type 1 diabetes. Based on both FTY720's action and the involvement of cellular infiltration in the disease progression, we tested FTY720 for its ability to prevent autoimmune diabetes in diabetes-prone, nonobese diabetic (NOD) mice. We found that treatment with FrY720 completely prevented NOD mice from developing autoimmune diabetes. The FTY720-treated animals showed both reduced numbers of circulating lymphocytes and sharply diminished cellular infiltration of pancreatic islets. These results suggest that FrY720 may be effective in prevention of autoimmune diabetes or in slowing its progression. (C) 2003 Elsevier Science (USA). All rights reserved.
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