The fever of gout: urate crystals activate endogenous pyrogen production from human and rabbit mononuclear phagocytes

Acute gout may be associated with fever but activation of EP production by crystalline urate in vivo has not been previously reported. We found that crystalline urate or silica stimulated macrophages but not PMNs to produce EP, without mediation by lymphocytes. The activation process did not require ingestion of the urate crystals, was unaffected by colchicine, and was not due to incidental LPS. Additionally, the failure of ingested latex particles to stimulate EP release indicated that phagocytosis alone was not a sufficient stimulus for EP production. We suggest that since EP and IL 1 are probably the same, the known inflammatory effects of IL 1, apart from fever induction, may contribute to the pathogenesis of acute gout and other crystal-associated human diseases.