Research Article| Volume 76, ISSUE 3, P472-479, September 1970

Anti-inflammatory effect of the trypsin-kallikrein inhibitor in acute arthritis induced by urate crystals in rabbits

  • Isaias Spilberg
    Reprint requests: Dr. I. Spilberg, Department of Preventive Medicine, Washington University School of Medicine, 4550 Scott Ave., St. Louis, Mo. 63110.
    From the Division of Arthritis and Connective Tissue Diseases, Department of Preventive Medicine and Department of Medicine, Washington University School of Medicine St. Louis, Mo. U.S.A.
    Search for articles by this author
  • C.Kirk Osterland
    From the Division of Arthritis and Connective Tissue Diseases, Department of Preventive Medicine and Department of Medicine, Washington University School of Medicine St. Louis, Mo. U.S.A.
    Search for articles by this author
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      This investigation sought to determine the effect of trypsin-kallikrein (T-K) inhibitor upon the inflammatory reaction induced by urate crystals in rabbits. Sodium urate crystals were injected into the skin and joints of rabbits. The resulting inflammatory response was substantially lessened when the T-K inhibitor was also injected. In vitro testing shows that the T-K inhibitor greatly reduced the proteolytic activity of polymorphonuclear lysosomal lysates at acid and neutral pH. Complement depletion of rabbits did not alter the joint inflammation resulting from injection of microcrystalline urate. It is suggested that the observed anti-inflammatory properties of the T-K inhibitor are related to its ability to inhibit acid and neutral polymorpho-nuclear lysosomal proteases and, to a lesser degree, to inhibition of kinin-forming enzymes. The evidence is reviewed which suggests that the proteases may be a major mediator of the inflammatory response in this model.
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