Comparative microbicidal activity of synovial fluid on arthritogenic organisms

There is strong circumstantial evidence to support the concept that local microbial antigens play a key role in the synovitis of reactive arthritis (ReA) patients. It is not at all clear whether these antigens reflect the sequelae of previously viable organisms once resident in the joint. To address the microbicidal activity of synovial fluid (SF) we performed quantitative cultures of arthritogenic organisms (Salmonella typhimurium, Shigella flexneri, Klebsiella pneumoniae) and controls (Escherichia coli, Staphylococcus aureus) in the presence of SF from patients with ReA. There was a dramatic inhibitory effect of SF on the Gram-negative organisms (mean 1.35x10(5) organisms at 3h; 0 organisms at 24 h) in contrast to Staph. aureus (1.61x10(5) at 3h; 5.70x10(5) at 24 h). This SF bactericidal phenomenon was observed in 11/11 ReA patients, 5/8 rheumatoid arthritis (RA) patients and 1/8 osteoarthritis (OA) patients. Using a sandwich ELISA, we measured SF levels of bactericidal/permeability-increasing protein (BPI). BPI was detectable in all ReA SF (range 4.6-333ng/ml)) and RA SF (range 343-2570ng/ml), but was absent in 5/6 OA SF tested. Anti-BPI antibodies, however, did not fully neutralize the bactericidal activity of inflammatory SF. In contrast to the SF effects observed on Gram-negative bacteria, Chlamydia trachomatis cultured within HeLa cells thrived in the presence of SF. Indeed extracellular Chlamydia could easily be passaged through cultured synovial fibroblasts in the presence of SF. These findings indicate that the potent microbicidal activity of SF may account for the failure to recover viable organisms from the joint in ReA. Chlamydia alone amongst these organisms demonstrates resistance to microbicidal effect of SF, which may relate to the pathogenesis of Chlamydia-induced arthritis.