IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin

Eric P.K. Mensah-Brown, Allen Shahin, Mariam Al-Shamisi, Xiaoging Wei, Miodrag L. Lukic

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

IL-23, a proximal regulator of IL-17, may be a major driving force in the induction of autoimmune inflammation. We have used a model of subdiabetogenic treatment with multiple low doses of streptozotocin (MLD-STZ; 4 × 40 mg/kg body weight) in male C57BL/6 mice to study the effect of IL-23 on immune-mediated β cell damage and the development of diabetes, as evaluated by blood glucose, quantitative histology, immunohistochemistry and expression of relevant cytokines in the islets. Ten daily injections of 400 ng IL-23, starting on the first day of MLD-STZ administration led to significant and sustained hyperglycemia along with weight loss compared with controls (no IL-23), and a significant increase in the number of infiltrating cells, a lower insulin content, enhanced apoptosis, expression of IFN-γ and IL-17 (not seen in the controls) and a significant increase in the expression of TNF-α and IL-18 in the pancreatic islets. IL-23 treatment started 5 days prior to MLD-STZ administration had no effect on diabetogenesis or cytokines expression in the pancreatic islets. We provide the first evidence in an animal model that IL-23 is involved in the development of type-1 diabetes, by inducing IL-17 and possibly IFN-γ production in the target tissue.

Original languageEnglish
Pages (from-to)216-223
Number of pages8
JournalEuropean Journal of Immunology
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • Diabetes
  • IFN-γ
  • IL-17
  • IL-23

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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