title: Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin.
abstract: 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.
authors.affiliation: Institute of Internal Medicine, University of Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Nicoletti
authors.forename: M O
authors.initials: MO
authors.lastname: Borghi
authors.forename: P L
authors.initials: PL
authors.lastname: Meroni
authors.forename: W
authors.initials: W
authors.lastname: Barcellini
authors.forename: C
authors.initials: C
authors.lastname: Fain
authors.forename: R
authors.initials: R
authors.lastname: Di Marco
authors.forename: R
authors.initials: R
authors.lastname: Menta
authors.forename: H U
authors.initials: HU
authors.lastname: Schorlemmer
authors.forename: G
authors.initials: G
authors.lastname: Bruno
authors.forename: G
authors.initials: G
authors.lastname: Magro
mesh_terms: 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
chemical_list: D006146:Guanidines; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D003520:Cyclophosphamide; C037258:gusperimus