Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes
Article first published online: 24 APR 2011
© 2011 John Wiley & Sons A/S
Volume 12, Issue 7, pages 656–667, November 2011
How to Cite
Sumpter, K. M., Adhikari, S., Grishman, E. K. and White, P. C. (2011), Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes. Pediatric Diabetes, 12: 656–667. doi: 10.1111/j.1399-5448.2011.00761.x
- Issue published online: 28 OCT 2011
- Article first published online: 24 APR 2011
- Submitted 5 November 2010. Accepted for publication 5 January 2011
- cDNA microarray analysis;
- gene expression;
- immunomodulatory therapy
Sumpter KM, Adhikari S, Grishman EK, White PC. Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes.
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.