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.
PREVENTION OF CYCLOPHOSPHAMIDE-INDUCED DIABETES IN THE NOD WEHI MOUSE WITH DEOXYSPERGUALIN
NICOLETTI, FERDINANDO;MAGRO, Gaetano Giuseppe;
1993-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
