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

Robert Z. Harms, Danielle N. Yarde, Zachary Guinn, Kristina M. Lorenzo-Arteaga, Kevin P. Corley, Monina S. Cabrera, Nora E. Sarvetnick

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)306-312
Number of pages7
JournalMolecular Immunology
Issue number2
StatePublished - Apr 1 2015


  • Autoimmune diabetes
  • Free IL-18
  • IL-18
  • IL-18BP
  • IL-37
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology


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