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.
ABSTRACT
<p><b>OBJECTIVE</b>To study the changes in hormone levels and the therapy of pituitary hyperplasia secondary to primary hypothyroidism in children.</p><p><b>METHODS</b>The clinical data of 8 children with pituitary hyperplasia secondary to primary hypothyroidism (5 girls and 3 boys) at ages of 5 to 9 years were studied retrospectively. All of the children had a short stature. They were followed up 1 to 6 years.</p><p><b>RESULTS</b>The thyroid hormone levels decreased and the serum thyroid stimulating hormone (TSH) and prolactin (PRL) levels increased in the 8 children. After 2 to 6 months thyroxine replacement therapy, the levels of free triiodothyronine (FT3), free thyroxine (FT4) and serum TSH and PRL returned to normal, and the pituitary enlargement regressed to normal in the 8 children. Of them, 6 children's height growth rate increased significantly from 3.1+/-0.5 cm per year to 11.6+/-1.7 cm per year (p<0.01). The other 2 cases had low growth rate and then received additional recombinant human growth hormone (rhGH) therapy. Their height growth rate increased by 11 cm per year. Pituitary hyperplasia did not recur in the 8 children during the follow-up.</p><p><b>CONCLUSIONS</b>The thyroid function and pituitary examinations are necessary for children with a short stature. Thyroxine substitution therapy appears to be effective for primary hypothyroidism secondary to pituitary hyperplasia. rhGH replacement therapy after regression of the pituitary enlargement can result in a satisfactory height growth in children with low thyroid hormone levels and growth hormone deficiency.</p>