Figure 2

CP-690,550 dose-dependently inhibits hind paw edema, PBNC, and serum inflammatory cytokine levels in the rat AIA model. AIA rats were treated orally with CP-690,550 (n = 12 rats per treatment group), twice daily, starting on day 14 and continuing through day 21 post-adjuvant immunization. Arthritis was monitored by measuring hind paw volume using volume displacement (A). (*) indicates statistical significance p < 0.014 compared to vehicle control treated disease animals. Drug exposure-paw volume response relationship was determined (B). CP-690,550 ED₅₀ plasma exposures were compared to in vitro rat whole blood IC₅₀ potencies for JAK1/2, JAK2, and JAK1/3 (C). Whole blood was analyzed for PBNC using a Cell-Dyne analyzer on day 21 post immunization (D). (*) indicates statistical significance p < 0.002 compared to vehicle control treated disease animals. IL-17 and IL-6 were quantitated using immunoassays (E). IL-17 (#) indicates statistical significance p ≤ 0.059 and IL-6 (*) indicates statistical significance p ≤ 0.013 compared to disease vehicle control. Day 21 dose-related correlation between reductions in hind paw edema and PBNC in AIA rats (F). Data represented as the mean ± SEM (A-D) or the mean percent control ± SEM (E and F).