Urate Crystal Induced Inflammation in the Rat: Evidence for the Combined Actions of Kinins, Histamine and Components of Complement

Abstract

The inflammation produced by subplantar injection of sodium urate micro-crystals in the hindpaw of the rat was used as a model of gouty arthritis. Kinins are probably involved since carboxypeptidase B or soybean trypsin inhibitor partially (35%) blocked the edema. Serotonin does not participate since the edema was not prevented by methysergide or cyproheptadine. Histamine is apparently involved since many antihistaminics also partially (40%) suppressed this edema. Two antihistaminics, promethazine and tri-pelennamine, inhibited (75%) the edema as effectively as colchicine by mechanisms as yet not established. Treatment of rats with a combination of soybean trypsin inhibitor and a specific antihistaminic, triprolidine, inhibited the urate edema by 58-66%, which suggested that still another mediator was involved. Complement depletion of the rats also partially (30%) inhibited the edema. The combination of soybean trypsin inhibitor, triprolidine and complement depletion almost completely (80%) suppressed the edema. In the rat, therefore, urate edema appears to be mediated by the combined actions of kinins, histamine and the components of complement.