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.
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 diabetespatients. 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.
Authors: Antoinette Moran; Brian Bundy; Dorothy J Becker; Linda A DiMeglio; Stephen E Gitelman; Robin Goland; Carla J Greenbaum; Kevan C Herold; Jennifer B Marks; Philip Raskin; Srinath Sanda; Desmond Schatz; Diane K Wherrett; Darrell M Wilson; Jeffrey P Krischer; Jay S Skyler; Linda Pickersgill; Eelco de Koning; Anette-G Ziegler; Bernhard Böehm; Klaus Badenhoop; Nanette Schloot; Jens Friis Bak; Paolo Pozzilli; Didac Mauricio; Marc Y Donath; Luis Castaño; Ana Wägner; Hans Henrik Lervang; Hans Perrild; Thomas Mandrup-Poulsen Journal: Lancet Date: 2013-04-05 Impact factor: 79.321