NEW YORK (Reuters Health) - Small interference RNA (siRNA) inhibition of interleukin-10 (IL-10) may translate into an improved host response against pathogens and tumors, according to a report in the June issue of the European Journal of Immunology.
Dr. John S. Yu and colleagues from Cedars-Sinai Medical Center, Los Angeles note that IL-10 suppresses the synthesis of Th1-derived cytokines by suppressing the maturation of antigen-presenting dendritic cells. siRNA specific for IL-10 might be useful in enhancing the Th1 immune response in dendritic cell-based cancer immunotherapy.
The researchers evaluated the potential application of a cellular vaccine system based on the suppression of endogenously expressed IL-10 to facilitate specific Th1 induction.
siRNA efficiently transfected dendritic cells without reducing their viability or maturation or inducing interferon expression, the authors report. IL-10 production was significantly inhibited and IL-12 expression increased. This resulted in significant increases in the induction of T cell proliferation.
Dendritic cells treated with IL-10 siRNA polarized naïve CD4 cells towards a Th1 immune response, the researchers note, as evidenced by increased production of interferon-gamma and lack of detectable production of IL-4.
“Transfection of dendritic cells with IL-10 siRNA is efficient and may offer the possibility of treating immune-based diseases in a specific and effective manner,” the authors conclude. They also point out the “the potential utility of this approach for dendritic cell-based cancer immunotherapy.”
In fact, Dr.Yu told Reuters Health, “we plan to translate this strategy to a preclinical model of brain glioma in mice and to translate it to a clinical trial.” We aim “to augment our phase II clinical trial by adding IL-10 siRNA to dendritic cells prior to vaccination for patients with glioblastoma.”
Source: Eur J Immunol 2004;34:1680-1687. [ Google search on this article ]
MeSH Headings:Biological Sciences: Biology: Gene Expression Regulation: Genetics: Genetics, Biochemical: Molecular Biology: RNA Processing, Post-Transcriptional: CD4-Positive T-Lymphocytes: RNA Editing: Th1 Cells: Th2 Cells: Biological SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
