Serum levels of the interferon-gamma-inducing cytokine interleukin-18 are increased in individuals at high risk of developing type I diabetes.
OBJECTIVE
Interleukin (IL)-18 is a cytokine primarily produced by macrophages and capable of inducing T lymphocyte synthesis of interferon (IFN)-gamma. An up-regulated synthesis of IFN-gamma with consequential Type I cytokine dominance has been repeatedly shown in Type I (insulin-dependent) diabetes mellitus and thought to be involved in its pathogenesis. Because increased production of IFN-gamma could be secondary to a dysregulated synthesis of IL-18, we compared the circulating levels of IL-18 in patients with newly diagnosed Type I diabetes with those of non-diabetic first-degree relatives and healthy control subjects.


METHODS
Serum samples were obtained from healthy control subjects, patients with newly diagnosed Type I diabetes, and their healthy first-degree relatives. The latter were subdivided into "low" and "high" risk prediabetics depending on whether they were negative or positive for two or more of the anti-pancreatic autoantibodies ICA, GAD, IA-2 and IAA. Serum levels of IL-18 were measured by solid-phase ELISA.


RESULTS
Interleukin (IL)-18 was above the detection limit of 25 pg/ml in 7 of 40 (17%) healthy control subjects, in 5 of 35 (14%) patients and in 3 of 30 (10%) first-degree relatives at low risk of developing Type I diabetes. In contrast, IL-18 could be detected in 19 of 28 (68%; p < 0.0001) relatives at high risk. The mean serum level of IL-18 was higher in these individuals when compared with the low-risk relatives, patients and control subjects.


CONCLUSIONS
IL-18 serum levels are increased selectively during the early, subclinical stage of Type I diabetes.
Nicoletti
F
F
Department of Clinical Medicine, Prevention and Biotechnological Health, University of Milan Bicocca, Italy.
Conget
I
I
Di Marco
R
R
Speciale
A M
AM
Morìnigo
R
R
Bendtzen
K
K
Gomis
R
R
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005190:Family; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D011236:Prediabetic State / Q000097:blood / Q000235:genetics / Q000276:immunology*; D012016:Reference Values; D018570:Risk Assessment
D001323:Autoantibodies; D015415:Biomarkers; C096322:ICA512 autoantibody; D020382:Interleukin-18; D005968:Glutamate Decarboxylase