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.
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http://dx.doi.org/10.1111/j.1365-2249.1993.tb05888.x | DOI Listing |
J Autoimmun
October 1994
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia.
Autoantibodies to glutamic acid decarboxylase (GAD) are present in humans before and after the onset of clinical insulin-dependent diabetes (IDD). The non-obese diabetic (NOD) mouse, a model of human IDD, develops mononuclear cell infiltration of the pancreatic islets ('insulitis') associated particularly in females with T cell-mediated destruction of the islet beta cells. In NOD mice of both sexes we detected serum antibodies to GAD (GAD Ab) that precipitate mouse brain GAD enzymatic activity.
View Article and Find Full Text PDFAutoimmunity
March 1995
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia.
Tumour necrosis factor (TNF) has been implicated in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). To investigate a possible role for TNF in IDDM we compared endogenous TNF production in two lines of non-obese diabetic (NOD) mice, NOD/Lt and NOD/WEHI, that have a high and low incidence of diabetes, respectively. Preliminary experiments had shown that the lower syngeneic mixed lymphocyte reaction (SMLR) in NOD/Lt mice could be corrected by TNF-alpha.
View Article and Find Full Text PDFEur J Immunogenet
October 1993
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia.
The basis for diabetes resistance in low diabetes incidence NOD/Wehi mice was examined in a breeding study. NOD/Wehi mice were crossed with high diabetes incidence NOD/Lt mice producing F1 hybrid mice which expressed a low incidence of diabetes. To distinguish between genetic and environmental causes for diabetes resistance, these F1 mice were backcrossed to NOD/Lt mice resulting in BC1 hybrid mice which expressed an intermediate incidence of diabetes.
View Article and Find Full Text PDFDiabetologia
August 1993
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
The non-obese diabetic (NOD) mouse is a spontaneous model of human insulin-dependent diabetes mellitus. Both CD4+ and CD8+ T cells infiltrate the pancreatic islets of NOD mice prior to beta-cell destruction. T-cell lines isolated from the islets of NOD mice are tools for studying the pathogenesis of insulin-dependent diabetes mellitus.
View Article and Find Full Text PDFClin Exp Immunol
February 1993
Institute of Internal Medicine, University of Milan, Italy.
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.
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