Cyclophosphamide inhibits the development of diabetes in the diabetes-prone BB rat
| Autor: | D. O. Sobel, Y.-H. Chung, B. Ahvazi, Ji-Won Yoon, Hee-Sook Jun |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Adoptive cell transfer Aging Cyclophosphamide Endocrinology Diabetes and Metabolism Cellular differentiation medicine.medical_treatment Spleen Lymphocyte Activation chemistry.chemical_compound Mice Mice Inbred NOD Diabetes mellitus Internal medicine Internal Medicine medicine Animals Rats Inbred BB Chemotherapy business.industry Reverse Transcriptase Polymerase Chain Reaction medicine.disease Nitrogen mustard Lymphocyte Subsets Rats Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 1 chemistry Cytokines business Insulitis Immunosuppressive Agents medicine.drug |
| Zdroj: | Diabetologia. 43(8) |
| ISSN: | 0012-186X |
| Popis: | Aims/hypothesis. Cyclophosphamide has been shown to augment the diabetic process in NOD mouse and BB rat models of Type I (insulin-dependent) diabetes mellitus. Because cyclophosphamide has, however, been shown to increase immunoregulatory cell activity, we examined if cyclophosphamide treatment increases immunoregulatory cell activity and inhibits the diabetic process in BB rats. Methods. The development of insulitis and diabetes was explored in BB rats treated with saline and cyclophosphamide (60 to 175 mg/kg body weight). Subsets of spleen cells were assessed by flow cytometry and cytokine gene expression by RT-PCR. To determine if cyclophosphamide induces immunoregulatory cell activity, the development of diabetes was assessed in BB rats injected with spleen cells from rats treated with saline and cyclophosphamide. Results. All dosages of cyclophosphamide decreased the development of diabetes. The degree of insulitis was lower in pancreata from 55-day-old rats treated with cyclophosphamide than those from controls. Cyclophosphamide caused no alterations in the numbers of NK cells, T-cell subsets, or RT6.1+ T cells. The adoptive transfer of spleen cells from cyclophosphamide-treated rats to BB rats inhibited the development of diabetes. Cyclophosphamide treatment decreased IL-12, IL-1β, IL-2, IFN-γ and TNF-α gene expressions in mononuclear spleen cells but IL-4 gene expression increased. Conclusion/interpretation. These findings show that cyclophosphamide treatment decreases the development of diabetes by inhibiting the development of insulitis. This inhibitory action of cyclophosphamide on the diabetic process seems to be mediated by the induction of immunoregulatory cell activity. The suppression of cytokines that promote Th1 cell differentiation by cyclophosphamide treatment could also play a part in the diabetes sparing effect of cyclophosphamide. [Diabetologia (2000) 43: 986–994] |
| Databáze: | OpenAIRE |
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