title: Protective role of adenovirus vector-mediated interleukin-10 gene therapy on endogenous islet β-cells in recent-onset type 1 diabetes in NOD mice.
abstract: The aim of the present study was to provide an animal experimental basis for the protective effect of the adenoviral vector-mediated interleukin-10 (Ad-mIL-10) gene on islet β-cells during the early stages of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. A total of 24 female NOD mice at the onset of diabetes were allocated at random into three groups (n=8 per group): Group 1, intraperitoneally injected with 0.1 ml Ad-mIL-10; group 2, intraperitoneally injected with 0.1 ml adenovirus vector; and group 3, was a diabetic control. In addition to groups 1, 2 and 3, 8 age- and gender-matched NOD mice were intraperitoneally injected with 0.1 ml PBS and assigned to group 4 as a normal control. All mice were examined weekly for body weight, urine glucose and blood glucose values prior to onset of diabetes, and at 1, 2 and 3 weeks after that, and all mice were sacrificed 3 weeks after injection. Serum levels of interleukin (IL)-10, interferon (IFN)-γ, IL-4, insulin and C-peptide were evaluated, and in addition the degree of insulitis and the local expression of IL-10 gene in the pancreas were detected. The apoptosis rate of pancreatic β-cells was determined using a TUNEL assay. Compared with groups 2 and 3, IL-10 levels in the serum and pancreas were elevated in group 1. Serum IFN-γ levels were decreased while serum IL-4 levels and IFN-γ/IL-4 ratio were significantly increased in group 1 (P<0.01). C-peptide and insulin levels were higher in group 1 compared with groups 2 and 3, (P<0.01). Furthermore, compared with groups 2 and 3, the degree of insulitis, islet β-cell apoptosis rate and blood glucose values did not change significantly (P>0.05). The administration of the Ad-mIL-10 gene induced limited immune regulatory and protective effects on islet β-cell function in NOD mice with early T1D, while no significant reduction in insulitis, islet β-cell apoptosis rate and blood glucose was observed.
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266001, P.R. China; Medical College, Qingdao University, Qingdao, Shandong 266071, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266001, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266001, P.R. China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266001, P.R. China.
authors.forename: Tang
authors.initials: T
authors.lastname: Li
keywords: immunotherapy; interleukin 10; non-obese diabetic mice; type 1 diabetes