Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat
| Autor: | Karen Kover, Wayne V. Moore, Figen Ugrasbul, Pei Ying Tong |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Stimulation Mycophenolate Gastroenterology Antibodies Treg depletion Internal medicine Diabetes mellitus Internal Medicine medicine Animals Rats Inbred BB IL-2 receptor Pancreas business.industry Interleukin-2 Receptor alpha Subunit Delayed treatment Mycophenolic Acid medicine.disease Rats Regimen Diabetes Mellitus Type 1 Autoimmune diabetes Pediatrics Perinatology and Child Health Immunology business |
| Zdroj: | Pediatric diabetes. 9(6) |
| ISSN: | 1399-5448 |
| Popis: | Background: Anti-CD25 and mycophenolate mofetil (MMF) treatment of patients with new-onset diabetes is currently being tested as one of the trials in TrialNet. We tested the effectiveness of MMF and anti-CD25 in preventing autoimmune diabetes in the diabetes-resistant biobreeding (DRBB) rat. Methods: Autoimmune diabetes in the DRBB rat was induced with a Treg cell depletion regimen starting at 24–26 d of age. Treatment was started on the first day of the depletion regimen in the following groups: (i) control (vehicle); (ii) MMF 25 mg/kg/d intramuscularly daily for 8 wk; (iii) anti-CD25 0.8 mg/kg/d intraperitoneally 5 d/wk for 3 wk; and (iv) combination of MMF and anti-CD25. In a second set of experiments, treatments were started on day 5 of the depletion regimen (delayed treatment) with groups 1, 3, and 4. Rats that had diabetes-free survival for at least 30 d after the treatment was stopped underwent a second Treg depletion (redepletion). Results: In each of the three treatment groups (n = 10/group), onset of diabetes was delayed or prevented in 20, 40 and 80% in groups 2, 3, and 4, respectively. After redepletion, diabetes-free survival was unchanged in group 2 and decreased to 10 and 30% in groups 3 and 4, respectively. With delayed treatment, groups 3 and 4 had 33 and 50% diabetes-free survival that decreased to 0 and 33% after redepletion. Summary: MMF and anti-CD25 alone or in combination are effective in delaying and preventing diabetes in the DRBB rat especially if treatment is started before stimulation and expansion of the autoreactive T cells. |
| Databáze: | OpenAIRE |
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