EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON CANINE NEUTROPHIL CHEMOTAXIS

Strøm, H. & Krogsgaard Thomsen, M. Effects of non‐steroidal anti‐inflammatory drugs on canine neutrophil chemotaxis. J. vet. Pharmacol. Therap. 13, 186–191. Non‐steroidal anti‐inflammatory drugs exhibit differences in their ability to suppress polymorphonuclear leucocyte (PMN) functions in different species. The present study investigated the in‐vitro and ex‐vivo effects of phenylbutazone and flunixin on leukotriene‐B4‐directed migration of canine PMN. Furthermore, in‐vitro comparison was made to indomethacin and the 5‐lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). In vitro, flunixin and NDGA were the most potent inhibitors, with IC50s of 13 and 7 μmol/l, respectively. Phenylbutazone had an IC50 of 42 μmol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 μmol/l. Ex vivo, flunixin almost completely abolished the LTB4 response at 1h, and still possessed significant inhibitory activity 24 h after a dosage of 1mg/kg i.v. Phenylbutazone was less active ex vivo but did suppress chemotaxis by 23% (P<0.05) at 1h following an i.v. dose of 20mg/kg. It is suggested that part of the anti‐inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment. M. Krogsgaard Thomsen, Department of Pharmacology, Leo Pharmaceutical Products, DK‐2750, Ballerup, Denmark. Copyright © 1990, Wiley Blackwell. All rights reserved