JAK2 blockade reduces several disease correlates in a model of chronic degenerative arthritis. Female DBA/1 mice were injected with purified CII in Complete Freund's Adjuvant (CFA) i.d., then boosted with CII in Incomplete Freund's Adjuvant (IFA) s.c. on day 21 followed by a day 28 LPS injection i.p. to induce collagen-induced arthritis (CIA). Mice that scored 1 or better for each paw were considered arthritic and entered into the study. Treatments started after 7 to 10 days of full arthritis. CEP-33779 was administered p.o., b.i.d., throughout the remainder of the experiment. Dex was administered i.p. at 1.5 mg/kg three times weekly, and vehicle was PEG400 + 1% DMSO p.o., b.i.d. (A) Mean paw size (individual paws measured) and clinical scores for each mouse are graphed. (B) Phospho-STAT3 expression in the paws of treated CIA mice. (C) Serum cytokines (IL-12, IL-2, IL-10 and TNFα) from treated CIA mice. (D) Representative ELISPOT images showing IFNγ enzyme-linked immunosorbent spot (ELISPOT) assay results from stimulated splenocytes from treated mice challenged with CII fragment (CB11), chicken ovalbumin (OVA) or media alone. Graph was constructed using data from five mice tested from each group. Spots were counted using a CTL ImmunoSpot ELISPOT scanner and spot-counting software. (E) Hematoxylin and eosin-stained, paraffin wax-embedded sections from treated CIA mice showing joint infiltrates and bone resorption. Representative (pathologist-selected) images are shown at × 10 original magnification. Safranin O-stain sections are not shown but were used for scoring. All graphs show means ± SEM, and all statistics were calculated using Prism software and two-way ANOVA. *P < 0.05. **P < 0.01. ***P < 0.001. Study size shows n ≥ 10 mice per group and n ≥ 5 mice for individual assays. Black arrows in parts A and C indicate treatment start.