title: Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes.
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.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Sumpter
authors.forename: Soumya
authors.initials: S
authors.lastname: Adhikari
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Grishman
authors.forename: Perrin C
authors.initials: PC
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D002096:C-Peptide / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D000078790:Insulin Secretion; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects
chemical_list: D018501:Antirheumatic Agents; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; C517652:hemoglobin A1c protein, human