STUDIES ON PHAGOCYTOSIS. II. THE EFFECT OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS ON PHAGOCYTOSIS AND ON URATE CRYSTAL-INDUCED CANINE JOINT INFLAMMATION

¹ Medical Research Laboratories, Pfizer, Inc., Groton, Connecticut

Phenylbutazone, indomethacin, sodium salicylate, gold sodium thiomalate and chloroquine were found to suppress polymorphonuclear leukocyte phagocytosis of starch granules in vitro. The threshold concentrations of these drugs at which activity was noted in the in vitro system were compared with plasma levels achieved in man under normal therapeutic doses. It was concluded that suppression of phagocytic function may be involved in the mechanism of action of these drugs. Indomethacin, phenylbutazone and acetylsalicylic acid were shown to suppress urate crystal-induced canine joint inflammation. The manner in which these compounds influenced the inflammatory response in vivo indicated a direct action on leukocytes, either by inhibition of phagocytosis or by interfering with inflammatory processes subsequent to the phagocytic event such as stabilization of phagolysosomes.