Increased expression of IL-18 in the serum and islets of type 1 diabetics

• Published in: Molecular immunology Vol. 64; no. 2; pp. 306 - 312
• Main Authors: Harms, Robert Z., Yarde, Danielle N., Guinn, Zachary, Lorenzo-Arteaga, Kristina M., Corley, Kevin P., Cabrera, Monina S., Sarvetnick, Nora E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2015
• Subjects: Adolescent; Autoimmune diabetes; Body Mass Index; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Female; Free IL-18; Gene Expression; Glycated Hemoglobin A - genetics; Glycated Hemoglobin A - immunology; Glycated Hemoglobin A - metabolism; Humans; IL-18; IL-18BP; IL-37; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - immunology; Interleukin-1 - blood; Interleukin-1 - genetics; Interleukin-1 - immunology; Interleukin-18 - blood; Interleukin-18 - genetics; Interleukin-18 - immunology; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Type 1 diabetes; Free IL-18; Autoimmune diabetes; IL-37; Type 1 diabetes; IL-18; IL-18BP
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2014.12.012

•We analyzed IL-18 levels in the plasma of juveniles with type 1 diabetes (T1D).•Increased IL-18 expression, but not IL-18BP or IL-37, was found in T1D vs. control.•Free IL-18 also determined to be significantly increased in T1D samples.•IL-18 and IL-18BP positively correlated to HbA1c levels in type 1 diabetics.•Significant increase in IL-18 protein expression in T1D human pancreatic islets.
Type 1 diabetes (T1D) is a chronic disease characterized by autoimmune-mediated destruction of pancreatic insulin-producing beta cells. Interleukin (IL)-18 is a pro-inflammatory cytokine implicated in the pathogenesis of a number of inflammatory diseases. Here, we analyzed IL-18 levels in the plasma of juveniles with T1D. Compared to control subjects, IL-18 levels were significantly elevated in patients with T1D. On the other hand, levels of IL-18 binding protein (IL-18BP) and IL-37, two negative regulators of IL-18 function, remained unchanged when comparing T1D to control samples. Notably, however, although IL-18BP levels were not elevated, IL-18 and IL-18BP were found to be positively correlated in type 1 diabetics. Even so, free, unbound IL-18 remained significantly increased in diabetic patients. Additionally, correlation studies also revealed that IL-18 and IL-18BP are positively correlated with HbA1c levels in T1D patients, suggesting a potential link between IL-18 and metabolic control in these patients. Finally, we observed a significant increase in IL-18 protein expression within human pancreatic islet specimens collected from type 1 diabetics. These results further expand our knowledge of the role of IL-18 in T1D, may give insight into common pathogenic mechanisms associated with metabolic control in both T1D and T2D, and suggest that targeting this cytokine may improve therapeutic outcomes for T1D patients.