Representative histologic staining (hematoxylin and eosin; ×100) of the ankle joints in mice with collagen-induced arthritis (CIA). At day 7 after the start of treatment with IFN-β, mice were sacrificed and subjected to histopathological examination. (a) In the control CIA mice treated with saline, massive cellular infiltration and erosion of bone were observed in the ankle joint. In CIA mice treated with the highest dose of IFN-β (2.5 μg per injection per mouse), limited hyperplasia of the intimal lining layer and cell infiltration of the synovial sublining were detected and a decrease in bone erosions was observed. (b) Infiltration of inflammatory cells of the joints was scored from 0 to 4 in a blinded manner as described in Materials and methods. A significant reduction in inflammatory cells was observed for the treatment groups treated with 2.5 μg and 1.25 μg IFN-β in comparison with controls (P = 0.04). *Statistically significant difference.