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

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 x 40 mg/kg body weight) in male C57BL/6 mice to study the effect of IL-23 on immune-mediated beta 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-gamma and IL-17 (not seen in the controls) and a significant increase in the expression of TNF-alpha 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-gamma production in the target tissue.

journal_name

Eur J Immunol

authors

Mensah-Brown EP,Shahin A,Al-Shamisi M,Wei X,Lukic ML

doi

10.1002/eji.200535325

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

216-23

issue

1

eissn

0014-2980

issn

1521-4141

journal_volume

36

pub_type

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