Histological changes in the knee joints of ob/ob and +/? mice during zymosan-induced arthritis (ZIA). (a) Histological changes were examined in zymosan A injected knee joints at an early (day 3) stage of ZIA. Representative sections stained with haematoxylin–eosin are shown for +/? (left panel; × 100) and ob/ob (right panel; × 100) mice. On day 3 we observed similar articular lesions in both +/? and ob/ob mice, which exhibited a moderate inflammatory cell infiltration associated with discrete synovial hyperplasia. (b) Histological changes were also examined in zymosan A injected knee joints at a late (day 21) stage of arthritis. A representative section stained with haematoxylin–eosin is shown for +/? mice in the left panel (× 100). On day 21 the joints of +/? mice exhibited only little inflammation, a discrete reactive synovial hyperplasia and a smooth cartilage surface. At this late stage some very severe cases of arthritis, with pronounced inflammatory cell infiltration and synovial hyperplasia, were observed exclusively in ob/ob mice, as illustrated in the right panel (haematoxylin–eosin; × 100). In this example, the articular cartilage has been largely destroyed and overgrown by a hyperplasic and inflammatory synovium. (c) Histological sections were scored for synovial hyperplasia, inflammatory cell infiltration and cartilage destruction. Cumulative total scores are shown for ob/ob (black columns) and +/? (white columns) mice at early (day 3: n = 9 per group) and late (day 14: n = 9–10 per group; day 21: n = 5 per group) time points after injection of zymosan A, representing histological changes during the early and chronic phases of ZIA, respectively. Data shown for each time point represent means ± SEM.