Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus

Aims  The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines. Subjects and methods  Forty‐two non‐diabetic first‐degree relatives of patients with Type 1 diabetes mellitus were re...

Full description

Saved in:
Bibliographic Details
Published in:Diabetic medicine 2006-02, Vol.23 (2), p.156-163
Main Authors: Hanifi-Moghaddam, P., Kappler, S., Seissler, J., Müller-Scholze, S., Martin, S., Roep, B. O., Strassburger, K., Kolb, H., Schloot, N. C.
Format: Article
Language:English
Subjects:
Autoantibodies - analysis
Biological and medical sciences
Chemokine CCL2 - blood
Chemokine CCL3
Chemokine CCL4
chemokines
Chemokines - blood
Chemokines, CC - blood
Cohort Studies
cytokines
Cytokines - blood
diabetes mellitus Type 1
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - immunology
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Humans
Interferon-gamma - blood
Interleukin-10 - blood
Interleukin-12 - blood
Interleukin-13 - blood
Interleukin-18 - blood
Interleukin-5 - blood
Islets of Langerhans - chemistry
Macrophage Inflammatory Proteins - blood
Medical sciences
pre-diabetes
Risk Factors
serum
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aims  The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines. Subjects and methods  Forty‐two non‐diabetic first‐degree relatives of patients with Type 1 diabetes mellitus were recruited. Of these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid decarboxylase antibody, IA‐2 antibody). Follow‐up for 9–11 years confirmed high vs. moderate diabetes risk in islet autoantibody‐positive vs. ‐negative relatives. Cytokines and chemokines were determined by enzyme‐linked immunosorbent assay (ELISA). Results  Serum concentrations of classic Th1‐associated cytokines (IFN‐γ, IL‐12, IL‐18) or Th2/Treg‐associated cytokines (IL‐5, IL‐10, IL‐13) did not significantly differ in high vs. moderate diabetes risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were increased (P = 0.0442 and P = 0.0334) while CCL2 was decreased (P = 0.0318) in the multiple islet autoantibody‐positive group. No significant differences were seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two closely related chemokines CCL3 and CCL4 in individuals at risk (r = 0.84, P = 0.00005), but not in the autoantibody‐negative group. Conclusion  Relatives at high risk of developing Type 1 diabetes mellitus have abnormal cellular immune regulation at the level of systemic chemokines. The up‐regulation of CCL3 and CCL4 vs. down‐regulation of CCL2 suggests opposed functions of these chemokines in the disease process. These findings need to be confirmed by independent studies.
ISSN:0742-3071
1464-5491
DOI:10.1111/j.1464-5491.2005.01743.x