Protective role of adenovirus vector-mediated interleukin-10 gene therapy on endogenous islet β-cells in recent-onset type 1 diabetes in NOD mice

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.