Protective effects of interleukin-10 and insulin-like growth factor-1 gene combination therapy on islet β cells of non-obese diabetic mice / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate whether IL-10 gene combined with insulin-like growth factor-1 (IGF-1)gene transfer could attenuate pancreatic insulitis,increase the percentage of CD4 + CD25 + Foxp3 + regulatory T cells,and protect β cells from autoimmune destruction.Methods An adenoviral vector containing IL-10 gene (Ad-IL-10) or IGF-1 gene(Ad-IGF-1) was constructed separately.Forty female non-obese diabetic (NOD) mice were injected intraperitoneally with Ad-IL-10 and/or Ad-IGF-1,Ad-green fluorescent protein(GFP) and phosphate buffered saline(PBS)separately,repeated after 3 weeks.Blood glucose concentration was measured weekly.Serum insulin,cytokine production were tested by enzyme-linked immunosorbent assay.CD4 + CD25 + Foxp3 + Treg cells were determined by flow cytometry.Pancreatic histology was measured for determination of insulitis grades.Pancreatic insulin content and β-cell mass,proliferation were measured.Apoptosis was measured by using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay.Results A significantly lower diabetes incidence (P ＜ 0.01) was observed in NOD mice treated with Ad-IL-10 and/or Ad-IGF-1,compared with mice treated with Ad-GFP or PBS alone,especially combined group.Lower insulitis score compared to control mice was found in Ad-IL-10 + Ad-IGF-1 group (all P ＜ 0.01).The serum level of TNF-α and IFN-γwere decreased and the level of IL-10 increased in combination therapy.The CD4 + CD25 +Foxp3 + cells was (7.17 ±0.38)％ in combined group,higher than that in the control groups.There was significantly less β-cell apoptosis(10.29 ±2.20)％ in combined group than that in other groups(all P ＜ 0.05).Conclusions Combination therapy with IL-10 and IGF-1 gene is able to increase the percentage of CD4 + CD25 + Foxp3 + regulatory T cells,reduce autoimmunity and increase pancreatic β-cell mass,indicating promising potential of these therapies as a new treatment strategy for diabetes mellitus.