Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin.
Ten out of 20 (50%) 17-week-old female NOD/WEHI mice developed an acute form of autoimmune diabetes when injected with two large doses of cyclophosphamide (CY), given at 14-day intervals. If these mice were treated under a prophylactic regimen with 2.5 mg/kg body weight per day of the novel immunosuppressant deoxyspergualin (DSP) the onset of diabetes was completely prevented. Moreover, DSP-treated animals showed reduced signs of pancreatic insulitis, had lower percentages of splenic lymphoid cells (SLC) expressing IL-2 receptors and Ly-6C antigens on their surfaces, and these cells released lower amounts of interferon-gamma (IFN) when stimulated in vitro. These data, providing evidence for the capacity of DSP to protect NOD/WEHI mice from experimental autoimmune diabetes and to modulate histo-immunological pathogenic pathways, indicate DSP as a drug of potential interest in the treatment of human insulin-dependent diabetes mellitus.
Nicoletti
F
F
Institute of Internal Medicine, University of Milan, Italy.
Borghi
M O
MO
Meroni
P L
PL
Barcellini
W
W
Fain
C
C
Di Marco
R
R
Menta
R
R
Schorlemmer
H U
HU
Bruno
G
G
Magro
G
G
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000517:prevention & control*; D003520:Cyclophosphamide / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use* / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000627:therapeutic use* / Q000633:toxicity; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D015375:Receptors, Interleukin-2 / Q000187:drug effects
D006146:Guanidines; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D003520:Cyclophosphamide; C037258:gusperimus