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

Diabet Med. 2006 Feb;23(2):156-63. doi: 10.1111/j.1464-5491.2005.01743.x.


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-gamma, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / analysis
  • Chemokine CCL2 / blood
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines / blood*
  • Chemokines, CC / blood
  • Cohort Studies
  • Cytokines / blood*
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / immunology
  • 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
  • Risk Factors


  • Autoantibodies
  • CCL2 protein, human
  • CCL4 protein, human
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines
  • Chemokines, CC
  • Cytokines
  • Interleukin-13
  • Interleukin-18
  • Interleukin-5
  • Macrophage Inflammatory Proteins
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma