Experimental gouty synovitis caused by bacterial endotoxin adsorbed onto urate crystals

Abstract

We used a laboratory model of gouty synovitis giving quantitative dosedependent 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.Why do acute attacks of gout occur so sporadically in patients who have persistent hyperuricemia? This question was asked by the late Dr. Gutman in a recent review on gout (1). Crystals of sodium urate are consistently demonstrable between attacks in joint aspirates of spontaneously occurring acute gouty arthritis, as shown by McCarty and Hollander (2), and yet such attacks are only sporadic. There must therefore be factors other than urate crystals essential to triggering the acute attack. Talbott states (3) that acute infections are frequent associates of gout, and that an acute pharyngitis may be complicated a few days later by acute articular distress.

Structural changes in sodium urate crystals on heating

“…Phelps and McCarty have found that MSU crystals heated at 200°C for 2 hours no longer activated complement (7), presumably due to the removal of pyrogens from the crystalline surfaces (8). Naff and Byers also noted that heated crystals no longer activated complement but, when heated crystals were dissolved and recrystallized, they regained their ability to deplete complement activity (9).…”

New knowledge of the pathogenesis of gout

“…The provocation of acute gout by infection or by the intravenous injection of bacterial pyrogen (Sicuteri 1968) led Van Arman et al (1974) to examine the effect of injecting into the joints of dogs urate crystals on to the surface of which had been absorbed endotoxin obtained from Escherichia coli. Such crystals produced a more severe synovitis than crystals free of endotoxin.…”

Chronic inflammation: Cellular events

“…Quantitatively the differences in purity might be only small, but qualitatively (as for example with a pyrogenic contaminant) the practical consequences may be far from small. This has been clearly documented by Van Arman et al in their studies of the effects of minute amounts of endotoxins on the oedemagenic/algesic activity of sodium urate crystals [1].…”