Adrenomedullin reduced joint swelling in rabbits with antigen-induced arthritis. Rabbits with antigen-induced arthritis (AIA) were treated with daily injections of adrenomedullin (AM) or saline (control) into the knee joint spaces beginning 24 hours after arthritis onset. Joint swelling was defined as the increase in knee diameter from normal and was compared with that at the same level on the contralateral knee, treated with saline. (a) Joint swelling progress in rabbits with AIA treated with daily intra-articular injections of AM or saline for 7 days (n = 5 in each group). Daily intra-articular injections of 3 μg AM significantly decreased joint swelling compared with contralateral knees after day 5. No significant decrease in joint swelling was observed in knees treated with <0.1 μg AM. (b) Joint swelling progress in rabbits with AIA treated with daily intra-articular injections of AM or saline for 20 days (n = 3 in each group). Daily intra-articular injections of 0.1 μg and 3 μg AM showed a tendency to reduce joint swelling throughout the experiment, and significantly decreased joint swelling on days 12 and 16 and on days 8, 12 and 16, respectively, compared with contralateral control knees. Daily intra-articular injections of 1 ng and 0.01 μg AM did not ameliorate joint swelling throughout the experiments (data not shown). Data expressed as the mean ± standard error of the mean. *P < 0.05 and **P < 0.01, compared with contralateral knees.