Superoxide anion production by monocytes and synovial fluid macrophages of patients with chronic inflammatory joint disorders.

Peripheral blood monocytes (PBMo) and synovial fluid macrophages (SFMO) of patients with rheumatoid arthritis (RA), HLA B27-positive reactive oligoarthritis and controls were investigated for their capacity to generate superoxide anions (O2-) upon stimulation with phorbolmyristoacetate (PMA) in a cytochrome c (cyt c) microassay. PBMo of RA patients, patients with reactive arthritis and controls did not reveal any significant differences and also treatment of RA patients with gold salts or immunosuppressive therapy had no effect on the oxidative burst in PBMo. In contrast, in SFMO of RA patients treated only with nonsteroidal anti-inflammatory drugs (NSAID) we found significantly enhanced O2- release, compared with PBMo of the same group. Treatment with gold salts had no effect on this enhanced oxidative response, whereas immunosuppressive therapy with azathioprin or corticosteroids significantly reduced the O2- release of SFMO. In patients suffering from reactive arthritis we did not find significant differences between SFMO and PBMo. The O2- release of SFMO of this group was significantly reduced, when compared to that of SFMO of RA patients, treated with NSAID. These results indicated that SFMO but not PBMo in RA in cyt c microassay produce increased levels of activated oxygen species. In comparison to PBMo, SFMO of patients suffering from reactive arthritis do not show such an increased oxidative burst. These findings suggest that in RA, activated oxygen species have a local destructive effect in inflamed joints. This seems to be caused by activation of catalytic enzymes and complement components, as well as induction of release of interleukins or prostaglandins, contributing to the augmentation of the chronic inflammatory process.