Abstract
Transgenic mice expressing interleukin 10 (IL-10) within the β cells of the pancreas were used to assess the role of this cytokine in the development of diabetes following low-dose streptozotocin treatment. Nontransgenic mice injected with low doses of streptozotocin were largely resistant to the induction of hyperglycaemia; that is, average blood glucose values, although above mean blood glucose levels of buffer-injected controls, did not exceed 14 mmol/l. In sharp contrast, IL-10 transgenic mice exhibited significant sensitivity to the diabetogenic actions of streptozotocin resulting in a mean blood glucose level of 21.6 mmol/l at the end of the 56-day study period. Histological analysis of pancreata from streptozotocin-injected transgenic mice revealed severe insulitis and destruction of pancreatic β cells, whereas their streptozotocin-injected nontransgenic littermates remained completely insulitis-free. According to immunocytochemical analysis, the pancreatic inflammatory infiltrates of streptozotocin-injected transgenic mice contained CD4+ and CD8+ T lymphocytes, B lymphocytes and macrophages. Furthermore, various adhesion molecules, the co-stimulatory molecule B7-1 and the Ia antigen could be detected. Splenocytes from streptozotocin-injected transgenic mice did not transfer disease to irradiated syngeneic nontransgenic recipients, suggesting that the presence of IL-10 in streptozotocin-injected mice had a general immunostimulatory effect but did not lead to the activation of P cell-specific T cells. Our data suggest a critical role for IL-10 in the development of diabetes in vivo despite its established immunosuppressive activities in vitro.
Original language | English (US) |
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Pages (from-to) | 151-158 |
Number of pages | 8 |
Journal | Journal of Autoimmunity |
Volume | 9 |
Issue number | 2 |
DOIs | |
State | Published - Apr 1996 |
Externally published | Yes |
Keywords
- Diabetes mellitus
- IL-10
- Insulitis
- Streptozotocin
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology