title: High T-helper-1 cytokines but low T-helper-3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes.
abstract: BACKGROUND
  Type 1 diabetes (T1D) is suggested to be of T-helper (Th)1-like origin. However, recent reports indicate a diminished interferon (IFN)-gamma secretion at the onset of the disease. We hypothesize that there is a discrepancy in subsets of Th-cells between children with a high risk of developing T1D, children newly diagnosed with T1D and healthy children.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMC) were collected from children at high risk for T1D (islet cells antibodies [ICA] >/= 20 IJDF-U), those newly diagnosed and healthy children carrying the HLA-risk gene DQB1*0302 or DQB1*0201 and DQA1*0501. Th1- (IFN-gamma, tumour necrosis factor [TNF]-beta, interleukin [IL]-2), Th2- (IL-4,-5,-13), Th3- (transforming growth factor [TGF-beta], IL-10) and inflammatory associated cytokines (TNF-alpha, IL-1alpha,-6) and chemokines (monocyte chemoattractant protein [MCP]-1,-2,-3, Monokine unregulated by IFN-gamma [MIG], Regulated on Activation, Normal T-cell Expressed and Secreted [RANTES], IL-7,-8,-15) were detected in cell-culture supernatants of PBMC, stimulated with glutamic acid decarboxylase 65 (GAD(65)) and phytohaemagglutinin (PHA), by protein micro array and enzyme linked immunospot (ELISPOT) technique.
  
  
  RESULTS
  The Th1 cytokines IFN-gamma and TNF-beta, secreted both spontaneously and by GAD(65)- and mitogen stimulation, were seen to a higher extent in high-risk children than in children newly diagnosed with T1D. In contrast, TNF-alpha and IL-6, classified as inflammatory cytokines, the chemokines RANTES, MCP-1 and IL-7 as well as the Th3 cytokines TGF-beta and IL-10 were elevated in T1D children compared to high-risk children.
  
  
  CONCLUSIONS
  High Th-1 cytokines were observed in children with high risk of developing TID, whereas in children newly diagnosed with T1D Th3 cytokines, inflammatory cytokines and chemokines were increased. Thus, an inverse relation between Th1-like cells and markers of inflammation was shown between children with high risk and those newly diagnosed with T1D.
authors.affiliation: Department of Paediatrics, 2nd Medical Faculty of Charles University, University Hospital Motol in Prague, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Stechova
authors.forename: Kristyna
authors.initials: K
authors.lastname: Bohmova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Vrabelova
authors.forename: Annelie
authors.initials: A
authors.lastname: Sepa
authors.forename: Gabriela
authors.initials: G
authors.lastname: Stadlerova
authors.forename: Klara
authors.initials: K
authors.lastname: Zacharovova
authors.forename: Maria
authors.initials: M
authors.lastname: Faresjö
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood; D018925:Chemokines / Q000097:blood; D002648:Child; D016207:Cytokines / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators