SUPPRESSIVE EFFECTS OF INDOMETHACIN ON CRYSTAL-INDUCED INFLAMMATION IN CANINE JOINTS AND ON NEUTROPHILIC MOTILITY IN VITRO

¹ The Rheumatology Research Laboratory, Philadelphia General Hospital and the Rheumatology Section, Department of Medicine, Rahnemann Medical College and Hospital, Philadelphia, Pennsylvania

Injection of monosodium urate crystals into the canine stifle joint induces an acute inflammatory reaction which is analogous to human gouty arthritis in many respects. Intraarticular pressure rises, reflecting fluid exudation; progressive fall in bulk pH of the exudate coincides with a progressive accumulation of polyrnorphonuclear leukocytes (PMN); local blood flow increase is reflected by an increased rate of clearance of Xe¹³³ injected into the joint. Indomethacin given i.v. or intraarticularly suppressed the increase in intraarticular pressure and Xe¹³³ clearance compared to control values in the same animals. PMN concentration per unit volume of synovial exudate was suppressed. As the total volume of exudate was decreased, it was obvious that the major effect of the drug was on PMN accumulation. It has been shown previously that the increase in intraarticular pressure in this system in PMN-dependent. The in vitro effect of indomethacin on PMN motility was tested using Boyden chambers, and a dose-related suppressive effect was found which persisted in washed leukocytes recovered from an animal given the drug i.v. It is postulated that one pharmacologic effect of indomethacin is through its effect on leukocyte motility.