Figure 2

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).