Transgenic expression of interleukin 10 in the pancreas renders resistant mice susceptible to low dose streptozotocin-induced diabetes

Regula Mueller, Myung Shik Lee, Stephen P. Sawyer, Nora Sarvetnick

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalJournal of Autoimmunity
Volume9
Issue number2
DOIs
StatePublished - Apr 1996

Keywords

  • Diabetes mellitus
  • IL-10
  • Insulitis
  • Streptozotocin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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