(a) Cytokine expression measured by immunohistochemistry after 7 days of systemic IFN-β treatment in mice with collagen-induced arthritis (CIA). Tumor necrosis factor (TNF)-α, IL-18, IL-1β, IL-10, and IL-6 were scored (mean ± SEM) in a blinded manner on a scale of 0 to 4 as described in Materials and methods. A statistically significant reduction of the proinflammatory cytokines TNF-α and IL-6 (P = 0.03 and 0.02, respectively) was observed in the mice treated with 2.5 μg IFN-β in comparison with controls. The expression of IL-18 and IL-1β was reduced in the animals treated with the highest dose of IFN-β, and the expression of IL-10 was higher than in controls. These differences did not reach statistical significance. No clear-cut differences were observed in the animals treated with 1.25 μg IFN-β in comparison with controls. Bars represent mice treated with 2.5 μg IFN-β (grey), 1.25 μg IFN-β (white) or saline (black). (b) Representative immunohistologic staining showing TNF-α expression in the ankle joints in CIA mice after 7 days of IFN-β treatment, assessed by immunohistochemistry. (Upper panel) TNF-α expression in CIA mice treated with saline; abundant expression of TNF-α was observed in the ankle joint. (Lower panel) TNF-α expression in CIA mice treated with 2.5 μg IFN-β; in the group treated with the highest dose of IFN-β, only a few positive cells for TNF-α were observed. *Statistically significant difference. SEM, standard error of the mean.