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)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha) and matrix metalloproteinase-9 (MMP-9) from ankle joints. CONCLUSIONS Macrophage elimination by SUVc inhibits local production of IL-1beta, IL-6, TNFalpha and MMP-9, and the pathogenesis of inflammatory arthritis.