Interleukin 10–knockout mice were highly susceptible to collagen-induced arthritis. (A) Graph illustrating the incidence of arthritis in interleukin 10–knockout (IL-10−/−) and wild-type (WT) mice. The incidence values were recorded on day (d) 30 after chicken type II collagen (CII) immunization. Values are representative of five independent experiments (n = 9 per group in each experiment). The mice were killed on day 45 or later postimmunization for immunological analysis and histopathologic examination. ( B) Graphed mean paw clinical arthritis severity scores (maximum possible score = 3) in IL-10−/− mice and WT mice with collagen-induced arthritis (CIA). Values are mean ± SEM (n = 45). *P < 0.05 vs. WT mice. (C) Histopathology images of the knee joints of IL-10−/− mice and WT mice with CIA (hematoxylin and eosin stain; original bar length = 200 μm). (D) Graphed evaluation results for synovitis, pannus and erosion of bone and cartilage in knee joint sections taken from IL-10−/− and WT arthritic mice (n = 3). (E) On day 45 following immunization, IL-10−/− and WT arthritic mice were bled and the concentrations of serum cytokines (IL-17, interferon γ (IFN-γ), IL-6 and IL-1β) of individual mice were determined by enzyme-linked immunosorbent assay (ELISA) (n = 3). (F) On day 45 following immunization, IL-10−/− and WT arthritic mice were bled and the serum levels of CII-specific immunoglobulin G2a (IgG2a) and IgG1 antibodies were measured by ELISA (n = 7). OD = Optical density. Horizontal lines indicate mean values. Data in (D) through (F) are mean ± SEM. *P < 0.05; **P < 0.01. NS = Not significant.