Synovial protease/inhibitor ratios in erosive and nonerosive arthropathies

Although rheumatoid joint fluids contain numerous polymorphs capable of secreting neutral proteases known to be able to digest cartilage, the high level of inhibitors (mainly alpha 1-antitrypsin and alpha 2-macroglobulin) has always been considered to be more than sufficient to inhibit their activity completely. Consequently little interest has been paid to the potential role of these enzymes in cartilage damage. Four arthropathies of different erosive potential are here compared: spondyloarthropathies, rheumatoid arthritis with and without gold or D-penicillamine therapy, and septic arthritis. The synovial concentration of the inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin has been compared with the polymorph enzyme output, as measured by beta-glucuronidase. Total haemolytic complement, white cell count, and C-reactive protein have also been measured in the joint fluid. The range of white cell count and inhibitors was the same in all 4 groups, while the enzyme output varied substantially from low levels in the spondyloarthropathies to very high levels in the septic joints. The higher the erosive potential of the disease, therefore, the more disadvantageous is the inhibitor/enzyme ratio. It is also pointed out that cartilage has physiochemical properties which facilitate and enhance polymorph enzyme output while severely curtailing the activity of the inhibitors. The observation that synovial fluid is inhibitory in vitro may therefore bear little relationship to the situation at the cartilage surface in vivo.