We used a laboratory model of gouty synovitis giving quantitative dose-dependent results with urate injection intrasynovially into the knee joint of dogs. We found that when precautions were taken to prevent any possible endotoxin contamination of the urate crystals, they became significantly less active. Endotoxin by itself, from Escherichia coli, was very potent in causing pain and leukocytic infiltration into the knee joint. Such endotoxin was readily and firmly adsorbed onto urate crystals. A small dose of urate crystals that caused no pain by itself became very painful when the crystals were allowed to adsorb endotoxin in vitro. When this same small non-painful dose of urate crystals was given into the joint, and the dog also received endotoxin by the oral route, signs of pain arose very clearly. It is known that gouty patients even when in remission may have crystals of sodium urate in the synovial fluid. It would therefore appear possible that if such urate crystals were to adsorb an endotoxin passing from the gastrointestinal tract into the plasma, thence into the synovial space, the patients may develop an attack of gout.
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