A monoarthritis model in rabbits induced by repeated intra-articular injections of lipopolysaccharide

We attempted to develop a monoarthritis model using repeated intra-articular injections of high-dose Lipopolysaccharide (LPS). Furthermore, the effect of dexamethasone on this arthritis model by intra-articular administration was studied to examine whether the model can be used to screen anti-rheumatic drugs in a short time. Arthritis was induced by one, two or three intra-articular injections of LPS (5-50 micrograms/joint) at 4-day intervals into the knee joint. The rabbits were sacrificed at 7 days following the last injection of LPS. Three intra-articular injections of LPS at 50 micrograms/joint resulted in persistent joint swelling. Hyperplasia of synovium with some discolouration was macroscopically observed. Infiltration of mononuclear cells and lymphoid follicles were histologically observed as the synovial lesions. Concerning the articular bone/cartilage, trabecular destruction of gastrocnemius sesamoid bone and severe loss of safranin-O staining of articular cartilage were observed. Immunohistochemical analysis revealed that inflammatory cells and lymphoid follicles in the synovial lesions consisted predominantly of CD4+ T cells, with few CD8+ T cells. Treatment with dexamethasone markedly reduced the joint swelling and the articular destruction. The results suggest that this arthritis model in rabbits can be utilized to screen anti-rheumatic drugs as a model of rheumatoid arthritis.