Studies on the mechanism of inflammation induced by calcium pyrophosphate crystals.

Abstract

Abstract This investigation sought to determine the role of complement, polymorphonuclear leukocytes, and lysosomal proteases in pseudogout. Acute skin and joint inflammation was induced in rabbits by injection of calcium pyrophosphate dihydrate crystals. When rabbits were depleted of complement with cobra venon before the injection of crystals, the inflammatory response was not affected, whereas leukocyte depletion of the rabbits with vinblastin significantly reduced the inflammatory response. The mixing of trypsin-kallikrein (T-K) inhibitor, an inactivator of acid and neutral lysosomal proteases and kallikrein, with the crystals prior to injection also reduced the inflammatory response. This effect of T-K inhibitor was dose-related. Soybean trypsin inhibitor, a stronger inhibitor of kallikrein than T-K, but with only weak effects upon lysosomal proteases, failed to alter the inflammatory process. Epsilon-amino caproic acid, an inhibitor of neutral but not acid protease, also failed to lessen the inflammation. The studies suggest that calcium phyrophosphate-induced inflammation requires normal levels of circulatory polymorphonuclear leukocytes, but does not depend upon complement and can be inhibited by the T-K inhibitor.