Intramuscular injection of interleukin-10 plasmid DNA prevented autoimmune diabetes in mice.
| Autor: | Zhang ZL; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China., Shen SX, Lin B, Yu LY, Zhu LH, Wang WP, Luo FH, Guo LH |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Acta pharmacologica Sinica [Acta Pharmacol Sin] 2003 Aug; Vol. 24 (8), pp. 751-6. |
| Abstrakt: | Aim: To investigate the effect of plasmid coding interleukin-10 (IL-10) DNA on the development of autoimmune diabetes induced by multiple low doses of streptozotocin (STZ) in mice. Methods: Injection of STZ (40 mg/kg, i.p.) was given daily for five consecutive days. pcDNA3-IL-10 plasmid (IL-10-treated group) or pcDNA3-null plasmid (pcDNA3-null-treated group) (100 microg DNA once a day) were injected into skeletal muscles of mice on d 1 and d 14. Blood glucose concentration was measured. After mice were killed on d 28, serum IFN-gamma level was measured by ELISA, and pancreatic IL-1beta and TNF-alpha mRNA expression was detected by semi-quantitative reverse-transcription PCR (RT-PCR). The number of CD4+ and CD8+ lymphocytes from spleen was detected using FACS. In addition, pancreatic histology was measured for determination of insulitis grades. Results: Treatment with pcDNA3-IL-10 resulted in the retention and expression of the vector in skeletal muscle, associated with a considerable elevation in the plasma level of IL-10, which was not observed in pcDNA3-null-treated mice. In IL-10-treated diabetic mice induced by STZ, delay-type hypersensitivity responses were suppressed and the glucose level was greatly lower on d 14, 21, and 28 than pcDNA3-null-treated group (P<0.05 or P<0.01). On d 21 and 28 the incidence of diabetes was 33.3% and 40.0%, respectively, which was markedly lower than that of pcDNA3-null-treated group (P<0.05). In IL-10-treated mice pancreatic IL-1beta and TNF-alpha mRNA expression was depressed, and serum IFN-gamma concentration and the number of spleen CD4+ or CD8+ lymphocytes were decreased on d 28. The insulitis grades of IL-10-treated mice were lower than that of pcDNA3-null-treated group (P<0.01). Conclusion: Systemic administration of IL-10 plasmid DNA can alleviate insulitis of experimental autoimmune diabetes in mice and reduce incidence of diabetes. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|