title: Increased expression of IL-18 in the serum and islets of type 1 diabetics.
abstract: 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.
authors.affiliation: Department of Surgery-Transplant, University of Nebraska Medical Center, 985965 NE Medical Center, Omaha, NE 68198-5965, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Harms
authors.affiliation: Department of Surgery-Transplant, University of Nebraska Medical Center, 985965 NE Medical Center, Omaha, NE 68198-5965, USA.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Yarde
authors.affiliation: Department of Surgery-Transplant, University of Nebraska Medical Center, 985965 NE Medical Center, Omaha, NE 68198-5965, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Guinn
authors.affiliation: Department of Surgery-Transplant, University of Nebraska Medical Center, 985965 NE Medical Center, Omaha, NE 68198-5965, USA.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Lorenzo-Arteaga
authors.affiliation: Pediatric Endocrinology, Children's Hospital & Medical Center, 8200 Dodge Street, Omaha, NE 68114, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Corley
authors.affiliation: Pediatric Endocrinology, Children's Hospital & Medical Center, 8200 Dodge Street, Omaha, NE 68114, USA.
authors.forename: Monina S
authors.initials: MS
authors.lastname: Cabrera
authors.affiliation: Department of Surgery-Transplant, University of Nebraska Medical Center, 985965 NE Medical Center, Omaha, NE 68198-5965, USA.|Holland Regenerative Medicine Program, University of Nebraska Medical Center, 985965 NE Medical Center, Omaha, NE 68198-5965, USA.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Sarvetnick
mesh_terms: D000293:Adolescent; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006442:Glycated Hemoglobin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male
chemical_list: D006442:Glycated Hemoglobin; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D020382:Interleukin-18; C000589760:IL18 protein, human; C508587:IL37 protein, human; C517652:hemoglobin A1c protein, human; C118370:interleukin-18 binding protein
keywords: Autoimmune diabetes; Free IL-18; IL-18; IL-18BP; IL-37; Type 1 diabetes