Blocking of IL-1 in mouse models of arthritis. (a) Inhibition of swelling. Mice were given different doses of ACZ885 or a control anti-CD25 antibody (CHI621, 12 mg/kg) intraperitoneally before injection of 10,000 3T3-huIL-1β cells into the right hind knee joint. Swelling was measured 3 days after cell injection (as described in Materials and methods) and is expressed as the ratio between the right (treated) and left (untreated) joint. The results presented represent the mean ± standard error or the mean (SEM; n = 5). **P < 0.01 by analysis of variance followed by Dunnett's test for multiple comparisons post hoc. NS, not significant. (b) Proteoglycan (PG) synthesis by chondrocytes in explanted patellae was measured by incorporation of 35S labelled sulphate in isolated cartilage from treated (right) and untreated (left) knee joints. The results are given as the ratio of 35S incorporation between right and left knee cartilage and represent the mean ± SEM (n = 5). Statistical analysis of the treated groups versus the control group (CHI621) was performed by analysis of variance followed by Dunnett's test for multiple comparisons post hoc. *P < 0.05; **P < 0.01. ED50, dose needed to achieve a mean of 50% effect. (c) Histology was analyzed at day 3 after local injection of 3T3-hIL-1β producing cells. Section of a mouse knee joint treated with isotype control antibody or AC885 are shown. Hematoxylin and eosin staining, original magnification (200×). Quantitative evaluation of the slides was done as described in Materials and methods and is presented in the graph. n = 5 joints per group; all comparisons between active and control were significant (P < 0.05, Mann-Whitney U-test).