PHAGOCYTIC SYNOVIAL LINING CELLS IN EXPERIMENTALLY-INDUCED CHRONIC ARTHRITIS - DOWN-REGULATION OF SYNOVITIS BY CL(2)MDP-LIPOSOMES

Chronic inflammation of the joint is characterized by the long-term pr esence of macrophage-like cells in the multilayered synovium. We exami ned whether synovial phagocytic cells which have settled in the inflam ed lining layer play a role in perpetuating synovitis by selectively e liminating them from chronically arthritic murine knee joints. For thi s purpose we used liposomes encapsulating the drug dichloromethylene d iphosphonate (CL(2)MDP, Clodronate). Injection of CL(2)MDP-liposomes i nto acutely inflamed knee joints (6 h, 1 and 3 days) had no significan t effect on late chronic synovitis (14 and 21 days after arthritis ind uction) as observed in haematoxylin and eosin-stained total knee joint sections. Liposomes did not reach the lining layer, as seen with fluo rescent liposomes. Additional in vitro studies revealed that activated polymorphs were not affected by CL(2)MDP-liposomes within 16 h of inc ubation. Liposomes formed clusters, however, in the presence of intact polymorphs or extracts of polymorphs. In contrast, a significant down -regulation of late synovitis was observed if CL(2)MDP-liposomes were given during the chronic phase (day 7). Phosphate-buffered saline (PBS ) alone or PBS-liposomes had no effect on synovitis. A single injectio n of CL(2)MDP-liposomes eliminated many of the phagocytic lining cells and deeper lying inflammatory cells for at least 4 weeks. Free CL(2)M DP had a minor but significant effect. This study indicates that phago cytic synovial lining cells play an important role in propagating chro nic synovitis. To eliminate them from inflamed knee joints, CL(2)MDP-l iposomes should be injected in the chronic and not in the early arthri tic phase.