Systemic TAK1-siRNA lipoplexes delivery alleviates inflammation in experimental autoimmune arthritis. DBA/1 mice were immunized with bovine type II collagen and boosted on day 21. Mice were intravenously administered (arrows) with 0.5 mg/kg of TAK1 siRNA (siTAK1). Control groups were injected with either PBS or a nontargeting control siRNA sequence (siCT). All siRNA duplexes were formulated with the cationic liposome, RPR209120/DOPE, and a DNA carrier, as described in “siRNA lipoplexes treatment.” (A) Mice with ongoing inflammation were administered with siTAK1 lipoplexes on days 30 and 44, and paw swellings were measured overtime. (B) From arthritis onset (day 23), mice were injected weekly with siCT or siTAK1 lipoplexes at the indicated time points. (C) HE (synovial inflammation; scale bar, 1 mm)–, safranin O/Fast green (cartilage erosion and proteoglycan loss; scale bar, 500 μm)–stained representative ankle-joint sections from experiment shown in B. (D) Histologic scores of synovial inflammation, cartilage erosion, and cartilage proteoglycan (PG) loss from the experiment shown in B. (E) Cytokine levels of TNF-α, IL-6, IL-12, and IL-23 in 24-hour conditioned media from the knee joints of control and TAK1 siRNA-treated mice were measured by ELISA at euthanasia. Results in panel A are the mean ± SEM of 10 mice per group, and results in panels B-E are the mean ± SEM of 7-8 mice per group. * P < .05, ** P < .01.