The immune modulator FYT720 prevents autoimmune diabetes in nonobese diabetic mice.
FTY720 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 1 diabetes is an autoimmune disorder caused by cellular-mediated destruction of insulin-producing pancreatic beta 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 FTY720 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 FTY720 may be effective in prevention of autoimmune diabetes or in slowing its progression.
Department of Internal Medicine, P.O. Box 801413, University of Virginia, Charlottesville, VA 22908, USA. zy4g@virginia.edu
Zandong
Z
Yang
Meng
M
Chen
Lawrence B
LB
Fialkow
Justin D
JD
Ellett
Runpei
R
Wu
Volker
V
Brinkmann
Jerry L
JL
Nadler
Kevin R
KR
Lynch
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D000068876:Fingolimod Hydrochloride; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011409:Propylene Glycols / Q000494:pharmacology*; D011897:Random Allocation; D013110:Sphingosine / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D007328:Insulin; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D005947:Glucose; D013110:Sphingosine