Abstract
Background: Interleukin-1β (IL-1β) may play a role in the pathogenesis of type 1 diabetes, but there are no data regarding the efficacy of agents antagonizing IL-1β in patients with this disorder. We characterized the effects of IL-1β on gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and gene expression effects of a short course of recombinant IL-1 receptor antagonist protein, anakinra, on children with newly diagnosed diabetes. Methods: PBMC from healthy adult volunteers were exposed to IL-1β for 24 h in vitro. Gene expression was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 diabetes received daily anakinra for 28 d and were followed for 6 months. Blood was drawn for microarray analysis before and after anakinra treatment. Insulin secretory capacity was assessed by mixed-meal tolerance testing (MMTT) at 3-4 wk and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were periodically recorded. Data were compared with two historical control groups of children with newly diagnosed diabetes. Results: Although in vitro exposure to IL-1β caused many changes in PBMC gene expression, gene expression did not change significantly after anakinra therapy in diabetes patients. Anakinra-treated patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 and 4 months after diagnosis compared to controls, and lower insulin-dose-adjusted A1c 1 month after diagnosis. Conclusions: Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.
Original language | English (US) |
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Pages (from-to) | 656-667 |
Number of pages | 12 |
Journal | Pediatric Diabetes |
Volume | 12 |
Issue number | 7 |
DOIs | |
State | Published - Nov 2011 |
Keywords
- CDNA microarray analysis
- Gene expression
- Immunomodulatory therapy
ASJC Scopus subject areas
- Internal Medicine
- Pediatrics, Perinatology, and Child Health
- Endocrinology, Diabetes and Metabolism