Suboptimal levels of hydrogen peroxide scavengers in synovial fluid: in vitro augmentation with slow acting antirheumatic drugs.

Phagocyte released reactive oxygen species are inflammatory mediators contributing to articular damage and potentially modulating local immune responses. We studied the protection afforded by synovial fluid (SF) against an important reactive oxygen species intermediate, hydrogen peroxide, quantitating SF-H2O2 scavenger levels and testing their functional capacity. Mean H2O2 scavenger levels in noninflammatory SF were low -3.9 mumol H2O2/ml-and similar to those found in plasma. Higher levels were found in inflammatory SF (24.6 mumol H2O2/ml), but still far below those found in whole blood (1,145.2 mumol H2O2/ml). SF with higher scavenger levels protected lymphocytes from H2O2 mediated damage and reversed lymphocyte suppression mediated by activated polymorphonuclear leukocytes. SF-H2O2 scavengers could be augmented by addition of certain blood cell subtypes, known enzymatic and chemical scavengers and also by several slow acting antirheumatic drugs. Our results indicate that the adaptive response of inflamed SF to reactive oxygen species is suboptimal. However it also appears that SF antioxidant levels could be augmented by certain slow acting antirheumatic drugs if sufficient tissue levels were obtained.