Suppression of chronic streptococcal cell wall‐induced arthritis in Lewis rats by liposomal clodronate

Objectives. To investigate the role of macrophages in the pathogenesis of chronic streptococcal cell wall (SCW)‐induced arthritis using liposomal clodronate. Methods. Female Lewis rats with SCW‐induced arthritis received a single intravenous injection of 20 mg of clodronate encapsulated within small unilamellar vesicles (SUVc) 10 days post‐arthritis induction. Results. SUVc significantly suppressed the development of chronic SCW‐induced arthritis for up to 26 days after treatment. At this time point, ED1+ macrophages were significantly depleted in the liver and ankle joints, although splenic macrophage numbers were not significantly different from control groups. Macrophage elimination induced a significant reduction in local levels of interleukin (IL)‐1β, IL‐6, tumour necrosis factor‐α (TNFα) and matrix metalloproteinase‐9 (MMP‐9) from ankle joints. Conclusions. Macrophage elimination by SUVc inhibits local production of IL‐1β, IL‐6, TNFα and MMP‐9, and the pathogenesis of inflammatory arthritis.