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 c hronic streptococcal cell wall (SCW)-induced arthritis using liposomal clod ronate. Methods. Female Lewis rats with SCW-induced arthritis received a single int ravenous injection of 20 mg of clodronate encapsulated within small unilame llar vesicles (SUVc) 10 days post-arthritis induction. Results. SUVc significantly suppressed the development of chronic SCW-induc ed arthritis for up to 26 days after treatment. At this time point, ED1(+) macrophages were significantly depleted in the liver and ankle joints, alth ough splenic macrophage numbers were not significantly different from contr ol groups. Macrophage elimination induced a significant reduction in local levels of interleukin (IL)-1 beta, IL-6, tumour necrosis factor-alpha (TNF alpha) and matrix metalloproteinase-9 (MMP-9) from ankle joints. Conclusions. Macrophage elimination by SUVc inhibits local production of IL -1 beta, IL-6, TNF alpha and MMP-9, and the pathogenesis of inflammatory ar thritis.