Journal
DIABETES
Volume 61, Issue 1, Pages 145-154Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db11-1033
Keywords
-
Categories
Funding
- National Institutes of Health [DK057846]
- Juvenile Diabetes Research Foundation (JDRF) [2009-694]
- Brehm Consortium
- SHARE LIFE initiative of the University of Copenhagen
- Novo Nordisk
- Canadian Institutes of Health Research
- Diabetes Association (Foothills)
Ask authors/readers for more resources
Inflammatory cytokines are involved in autoimmune diabetes: among the most prominent is interleukin (IL)-1 beta. We postulated that blockade of IL-1 beta would modulate the effects of anti-CD3 monoclonal antibody (mAb) in treating diabetes in NOD mice. To test this, we treated hyperglycemic NOD mice with F(ab')(2) fragments of anti-CD3 mAb with or without IL-1 receptor antagonist (IL-1RA), or anti-IL-1 beta mAb. We studied the reversal of diabetes and effects of treatment on the immune system. Mice that received a combination of anti-CD3 mAb with IL-1RA showed a more rapid rate of remission of diabetes than mice treated with anti-CD3 mAb or IL-1RA alone. Combination-treated mice had increased IL-5, IL-4, and interferon (IFN)-gamma levels in circulation. There were reduced pathogenic NOD-relevant V7 peptide-V7(+) T cells in the pancreatic lymph nodes. Their splenocytes secreted more IL-10, had increased arginase expression in macrophages and dendritic cells, and had delayed adoptive transfer of diabetes. After 1 month, there were increased concentrations of IgG1 isotype antibodies and reduced intrapancreatic expression of IFN-gamma, IL-6, and IL-17 despite normal splenocyte cytokine secretion. These studies indicate that the combination of anti-CD3 mAb with IL-1RA is synergistic in reversal of diabetes through a combination of mechanisms. The combination causes persistent remission from islet inflammation. Diabetes 61:145-154, 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available