FIGURE 4

2'-O-methyl (2'OMe) RNA inhibits single-stranded RNA (ssRNA) and loxoribine-mediated cytokine production in vivo. (a) Interferon-(IFN-) and (b) interleukin-6 (IL-6) induction in mice treated with either immunostimulatory ssRNA (gal AS), 2'OMe RNA [(mU)₂₁] or gal AS + (mU)₂₁ formulated at a 1:1 molar ratio in lipid particles. Plasma cytokines were measured 6 hours after intravenous administration of formulations containing 40 g gal AS RNA. (c–f) Treatment of mice with 2'OMe RNA inhibits (c, e) IFN- and (d, f) IL-6 induction by loxoribine (Lox). Mice received 100 g formulated (mU)₂₁ 2 hours before the administration of 1 mg soluble Lox in phosphate-buffered saline (PBS). Control groups were pre-treated with either (c, d) PBS or (e, f) 100 g formulated GFP-S RNA, a native ssRNA with negligible immunostimulatory activity. Plasma IFN- and IL-6 levels 2 hours after intravenous Lox administration were significantly reduced in (mU)₂₁-treated mice compared with mice receiving either PBS or formulated control RNA. Data are mean + SD of n = 4 mice per group and are representative of two separate experiments. GFP, green flourescent protein