The inhibitory oligonucleotides with partial phosphorothioation with reduced toxicity strongly block NF-kB activation induced by TLR9 agonists and TLR7/8 agonists. The production of proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa), is inhibited by the inhibitory-oligonucleotides. Interferon (IFN) production from human PBMC induced by TLR9 agonist is prevented by the inhibitory-oligonucleotides. These oligonucleotides can be used as a remedy for the treatment of immune-mediated disorders such as rheumatoid arthritis, systemic lupus erythematosus (SLE), sepsis, multiple organ dysfunction syndromes and inflammatory cytokine-mediated inflammatory disease.
