AIMS/HYPOTHESIS: 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/ INTERPRETATION: IL-18 serum levels are increased selectively during the early, subclinical stage of Type I diabetes.
AIMS/HYPOTHESIS: 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/ INTERPRETATION:IL-18 serum levels are increased selectively during the early, subclinical stage of Type I diabetes.
Authors: Peter A Gottlieb; Aimon K Alkanani; Aaron W Michels; Eli C Lewis; Leland Shapiro; Charles A Dinarello; Danny Zipris Journal: J Clin Endocrinol Metab Date: 2014-02-14 Impact factor: 5.958
Authors: A E Altinova; D Engin; E Akbay; M Akturk; F Toruner; R Ersoy; I Yetkin; M Arslan Journal: J Endocrinol Invest Date: 2009-12-22 Impact factor: 4.256