Effect of folate-targeted immunotherapy on joint inflammation and bone/cartilage destruction in AIA rats. Where indicated, AIA rats were immunized with a 1:1 suspension of keyhole limpet hemocyanine-fluorescein isothiocyanate (KLH-FITC) and TiterMax Gold adjuvant to generate a high anti-FITC antibody titer. On day 0, rats were induced to develop AIA via the footpad method. (a) Treatments began on the day of arthritis induction, and rats were given i.p. doses twice a week at 375 nmole folate-FITC/kg. Treatment groups included: AIA rats not immunized and not treated (No Treatment), non-immunized rats treated with folate-FITC (Folate-FITC), AIA rats immunized against fluorescein and treated with non-targeted aminofluorescein (KLH-FITC + AF), AIA rats immunized against fluorescein and treated with folic acid alone (KLH-FITC + Folate), AIA rats immunized against fluorescein but not further treated (KLH-FITC), AIA rats immunized against fluorescein and treated with folate-FITC (KLH-FITC + folate-FITC [FTI]), AIA rats treated on days 8, 16, and 23 with 3.6 mg/kg clodronate liposomes (CL), AIA rats treated with methotrexate (MTX; 0.75 mg/kg per week, i.p.), immunized healthy rats (KLH-FITC + Healthy), and untreated healthy rats (Healthy), respectively. Data are representative of two independent experiments (n = 5 rats/group; [folate-FITC] vs. [KLH-FITC + folate-FITC (FTI)], p < 0.01). The impact on bone and cartilage degradation was assessed both by analysis of radiological (RAD) scores (b) and visual inspection (c) on day 25 after arthritis induction (mean ± standard deviation, n = 4 or 5 rats/group). Data are representative of three independent experiments. (RAD scores: folate-FITC vs. KLH-FITC + folate-FITC (FTI), p < 0.05).