title: Role of interleukin-1/interleukin-1 receptor antagonist family of cytokines in long-term continuous glucose monitoring in vivo.
abstract: BACKGROUND
  Glucose-sensor-induced tissue reactions (e.g., inflammation and wound healing) are known to negatively impact sensor function in vivo. The roles of cytokine networks in controlling these tissue reactions (i.e., sensor biofouling) is not understood. In the present study, we investigated the role of interleukin-1 receptor antagonist (IL-1Ra), a key anti-inflammatory antagonist of the proinflammatory interleukin-1 cytokines [i.e. interleukin-1 (IL-1) alpha and IL-1 beta] in controlling continuous glucose monitoring (CGM).
  
  
  METHODS
  To investigate the role of IL-1Ra in long-term CGM in vivo, we compared CGM in transgenic mice that overexpress IL-1Ra [interleukin-1 receptor antagonist overexpresser (IL-1Ra~OE), B6.Cg-Tg(IL1rn)1Dih/J] or are deficient in IL-1Ra [interleukin-1 receptor antagonist knockout (IL-1Ra~KO), B6.129S-IL1rn(tm1Dih)/J] with mice that have normal levels of IL-1Ra (C57BL/6) over a 28-day time period.
  
  
  RESULTS
  Mean absolute relative difference (MARD) analysis of CGM results among the mice of varying IL-1Ra levels demonstrated that during the first 21 days, IL-1~KO mice had the greatest tissue inflammation and the poorest sensor performance (i.e., higher MARD values) when compared with normal or IL-1Ra~OE mice. By 28 days post-sensor implantation, the inflammatory reactions had subsided and were replaced by varying degrees of fibrosis.
  
  
  CONCLUSIONS
  These data support our hypothesis on the importance of the IL-1 family of agonists and antagonists in controlling tissue reactions and sensor function in vivo. These data also suggest that local delivery of IL-1Ra genes or recombinant proteins (anakinra) or other IL-1 antagonists such as antibodies or soluble IL-1 receptors would suppress sensor-induced tissue reactions and likely enhance glucose sensor function by inhibiting inflammation and wound healing at sensor implantation sites.
authors.affiliation: Center for Molecular Tissue Engineering, University of Connecticut School of Medicine, Farmington, CT. klueh@nso.uchc.edu.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Klueh
authors.forename: Omar
authors.initials: O
authors.lastname: Antar
authors.forename: Yi
authors.initials: Y
authors.lastname: Qiao
authors.forename: Donald L
authors.initials: DL
authors.lastname: Kreutzer
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation* / Q000379:methods; D016207:Cytokines / Q000502:physiology*; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D019736:Prostheses and Implants / Q000009:adverse effects; D015203:Reproducibility of Results; D014945:Wound Healing / Q000502:physiology
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1