PHAGOCYTIC SYNOVIAL LINING CELLS IN PROPAGATION AND EXACERBATION OF SMOLDERING SYNOVITIS

We investigated the in vivo role of phagocytic synovial lining cells ( SLC) in sustaining synovial inflammation during chronic arthritis and their function in exacerbation of smouldering synovitis in the mouse. Phagocytic SLC were depleted by a single injection of multilamellar li posomes containing the drug dichloromethylene diphosphonate (clodronat e). Liposomes are preferentially taken up by macrophages and the drug is released within the cell in large amounts. Within a few days macrop hages are removed from the joint. A single injection of clodronate lip osomes given into the knee joint, 7 days after induction of antigen-in duced (mBSA) arthritis stripped the thickened lining for the greater p art. Optimal elimination was observed 7 days after liposome injection. No recovery of the synovitis was observed thereafter. In addition rea ctivation of synovitis was induced by giving 350 mu g mBSA intravenous ly. In SLC depleted arthritic knee joints, a significant decrease in f lare was observed if compared to control, PBS injected arthritic knee joints. IL-1 levels which are elevated 6 h after induction of the flar e were also significantly reduced in SLC depleted arthritic joints. Ou r data indicate that phagocytic SLC are directly involved in propagati on and exacerbation of chronic synovitis.