Figure 5

PCI-32765 dose-dependently inhibits disease in the CAIA, Arthus, and PCA models. (a) Mice (n = 10) were treated with PCI-32765 orally once daily. Daily average clinical scores are plotted over 14 days of treatment; ***P < 0.001 (Student t-test). (b) Tissue sections from six joints (carpus, tarsus, and knee) of treated mice stained with H&E and Safranin-O were evaluated through histopathology for inflammation, pannus, cartilage damage, and bone erosion (n = 10). PCI-32765 treatments significantly inhibited inflammation, pannus, cartilage, and bone damages. (c) Representative reconstructed micro-CT images of forelimb of mice treated with vehicle, PCI-32765 (12. 5 mg/kg) or dexamethasone (0.2 mg/kg). (d) Mean J scores of bone destruction calculated from micro-CT images (n = 3). (e) PCI-32765 treatments were evaluated in Arthus reactions induced by OVA and anti-OVA injections. Evans blue dye extravasation area measurements (left) and tissue biopsies evaluated for change of OD (right) are shown (n = 6). (f) PCI-32765 inhibits anti-DNP (dinitrophenol)-IgE and DNP-BSA mediated skin PCA. Extravasation area (left panel) and change of Evans blue OD (optical density) measurements (n = 10) (right panel) are displayed. * P < 0.05, ** P < 0.01; *** P < 0.001 compared with vehicle, analysis of variance. CAIA, collagen antibody-induced arthritis; OVA, ovalbumin; PCA, passive cutaneous anaphylaxis.