Effect of bosentan on antigen-induced arthritis (AIA) flare-up reactions. (a) Schematic drawing of experimental setup. Animals were immunized 21 and 14 days before induction of AIA. Mice received repeated oral applications of either 100 mg/kg bosentan or saline (Control) every 24 hours for 42 days beginning 2 hours before the initial induction of AIA. AIA flare-up reactions were provoked on days 21 and 35. Joint swelling was assessed as indicated. All animals were tested twice during the immunization procedure to obtain baseline values depicted as day 0. After 3, 21, or 42 days, mice were killed, and affected knee joints were prepared for histological scoring. (b) Inhibition of knee joint swelling by bosentan during AIA flare-up reactions. Knee joint swelling as an indicator of inflammation was assessed by measuring the mediolateral diameter of each knee. Values in (b) are means ± standard error of the mean. The results from two-way analysis of variance followed by the Bonferroni post hoc test are shown (*P < 0.05; ο, not significant). p.o., per os (by mouth).