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Interleukin-6 small interfering RNA improved the herpes simplex virus-induced systemic inflammation in vivo Behcet's disease-like mouse model.

Authors
Shim, J; Byun, HO; Lee, YD; Lee, ES; Sohn, S
Citation
Gene therapy, 16(3):415-425, 2009
Journal Title
Gene therapy
ISSN
0969-71281476-5462
Abstract
It is known that the level of interleukin-6 (IL-6) is higher in patients with active Behcet's disease (BD) than in those with inactive disease. Herpes simplex virus (HSV) type 1 inoculation of the earlobes of ICR mice resulted in the development of BD-like symptoms. To find out whether downregulation of IL-6 would affect the symptoms of BD, IL-6 small interfering RNA (siRNA) was administered to a BD mouse model. IL-6 siRNA was intraperitoneally injected into BD mice to downregulate IL-6 (n=9). IL-6 siRNA injection downregulated serum IL-6 level (118.9+/-114.4 pg ml(-1)) compared with scramble injection (439.4+/-378.0 pg ml(-1)) in BD mice (P=0.01). In seven out of nine IL-6 siRNA-injected BD mice, 77.8% improved and the severity score was decreased from 3.1+/-1.05 to 1.7+/-0.87 (P=0.005), whereas two out of six (33.3%) scramble-injected BD mice improved and the severity score changed from 2.5+/-0.84 to 2.0+/-1.41 (P=0.203). Foxp3, ROR gamma t, IL-17A, IL-17F and tumor necrosis factor-alpha were also influenced in IL-6 siRNA-injected BD mice compared with scramble-injected BD mice. Adoptive transfer of CD4+CD25+ cells to BD mice affected the decrease of IL-6 serum levels and were dependent on CD4+CD25+ cell numbers. These results showed that downregulation of IL-6 improved the inflammatory symptoms in BD mice through upregulation of regulatory T cells and inhibition of Th17 cells.
MeSH terms
Adoptive TransferAnimalsBehcet Syndrome/geneticsBehcet Syndrome/immunologyBehcet Syndrome/therapy*Behcet Syndrome/virologyDisease Models, AnimalDown-Regulation/geneticsDown-Regulation/immunologyGene Therapy/methods*Herpes Simplex/complications*Herpesvirus 1, HumanInterleukin-17/biosynthesisInterleukin-23/biosynthesisInterleukin-6/biosynthesisInterleukin-6/genetics*MaleMiceMice, Inbred ICRRNA Interference/immunologyRNA, Small Interfering/genetics*T-Lymphocytes, Regulatory/immunologyTransforming Growth Factor beta/bloodTreatment OutcomeTumor Necrosis Factor-alpha/bloodUp-Regulation/geneticsUp-Regulation/immunology
DOI
10.1038/gt.2008.180
PMID
19092856
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Journal Papers > School of Medicine / Graduate School of Medicine > Dermatology
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
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