Protease inhibitors ininflammatory synovial effusions

SUMMARY Granulocyte lysosomal enzymes can potentially participate incartilage degradation in inflammatory arthritides. However, we havepreviously shownthatthequantity ofseveral such enzymes inan inflammatory synovial effusion correlates negatively withthedegree ofradiographic damageofthejoint fromwhichthefluid was sampled. Inthecurrent workthequantity ofthefollowing 5protease inhibitors was determined immunochemically inthesame fluids: al antitrypsin, aoc-antichymotrypsin, M2-macroglobulin, inter-a-trypsin inhibitor, andCl esterase inhibitor. Theseinhibitors aregenerally covariate andcorrelate positively withthetotal protein inthefluid aswell asthenumberofgranulocytes andtheconcentration ofgranulocyte lysosomal enzymesinthefluid. Asdidthelysosomal enzymes,theprotease inhibitors correlate negatively with radiographic destruction. Itislikely thatlysosomal enzymes insolution ininflammatory synovial effusions arerendered effete bythepresenceofprotease inhibitors. Onetheory ofthepathogenesis ofarticular destructioninrheumatoid arthritis holdsthatpolymorphonuclear neutrophil (PML)lysosomal enzymes in solution intheinflammatory synovial fluid are primarily responsible forcartilage degradation.' If this wereso,onewouldpredict thatthequantity of activePML lysosomal enzymes insynovial fluid would correlate withthedegree ofjoint destruction. Ina recent study2 we havetested this corollary hypothesis. By9immunochemical andenzymatic assays wequantitated 5different granulocytic enzymes in synovial fluids from36patients. We aresampling a single point intimeinaspectrum ofdisease with considerable chronicity andvariability. Nonetheless apopulation ofthis size allows ustotesta null hypothesis (anabsence ofcorrelation between the quantity ofenzymes andthedegree ofradiographic destruction ofthejoint sampled) withsomeconfidence. Wewereable toreject this null hypothesisbutthecorrelation we observed wasnegative. In other words, thegreater thequantity ofenzymes we detected, theless likely wasthefluid sampled froma radiographically damaged joint. Thisunexpected result raises 2important questions: Sincehumanlysosomal enzymeshavethe