Induction of interleukins IL-6 and IL-8 by siRNA

Induction of interleukins IL-6 and IL-8 by siRNA

Online publication: 01/01/2007


The HIV-1 co-receptor CCR5 has been thought a relevant target for small
interfering RNA (siRNA)-based therapeutics. However, recent findings
suggest that siRNA can stimulate innate cytokine responses in mammals. All
siRNA agents tested were able to down-regulate the expression of CCR5, albeit
with different efficiency (51–74% down-regulation), block HIV-induced syncytia
formation between HIV-1 BaL-infected and uninfected CD4+ cells or
block single-round HIV-1 infection as measured by a luciferase reporter assay
(46–83% inhibition). Conversely, siRNA directed against CCR5 did not affect
replication of a vesicular stomatitis virus (VSV) pseudotyped virus, suggesting
that inhibition of HIV replication was specific to CCR5 down-regulation.
However, two of four siRNA tested were able to induce the production of
interleukin (IL) IL-6 (sixfold induction) and IL-8 (ninefold induction) but no
interferon (IFN)-a, IFN-b, IFN-g, tumour necrosis factor (TNF)-a,monocyte
chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-
1a, MIP-1b,RANTES, IL-1b, IL-10 or IL-12p70 cytokine induction was noted.
In the absence of detectable IFN-a, IL-6 or IL-8 may represent markers of
non-specific effects triggered by siRNA.

Authors: Pauls, E., Senserrich, J., Bofill, M., Clotet, B., Esté, J.A.
  • Doi Code: Clinical and Experimental Immunology, 147: 189-196

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