Quantification of protease activities in synovial fluid from rheumatoid and osteoarthritis cases: comparison with antioxidant and free radical damagemarkers

We have compared (using the same series of experimental samples) the levels of activity of a comprehensive range of cytoplasmic, lysosomal and matrix protease types, together with the levels of free radical-induced protein da mage (determined as protein carbonyl derivative) in synovial fluid from rhe umatoid (RA) and osteoarthritis (OA) cases. Many protease types showed sign ificantly increased activity (typically by a factor of 2-3-fold) in RA comp ared to OA cases. Protease activity levels (including those enzyme types pu tatively involved in the immune response, such as dipeptidyl aminopeptidase IV) in plasma were not significantly different in RA and control cases. Th e level of free radical induced damage to synovial fluid proteins was appro ximately 2-fold higher in RA compared to OA, although there was no signific ant difference in total antioxidant status in synovial fluid or plasma betw een RA, OA or control cases. We conclude from the above that activation of proteolytic enzymes and free radicals (occurring specifically within synovi al tissues) are likely to be of equal potential importance as protein damag ing agents in the pathogenesis of RA, and the development of novel therapeu tic strategies for the latter disorder should include both protease inhibit ory and free radical scavenging elements. In addition, the protease inhibit ory element should be designed to inhibit the action of a broad range of en zymic mechanistic types (cysteine, serine, metallo proteinases and peptidas es). (C) 1999 Elsevier Science B.V. All rights reserved.