Effects of non-steroidal anti-inflammatory drugs on canine neutrophil chemotaxis.
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 mumol/l, respectively. Phenylbutazone had an IC50 of 42 mumol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 mumol/l. Ex vivo, flunixin almost completely abolished the LTB4 response at 1 h, and still possessed significant inhibitory activity 24 h after a dosage of 1 mg/kg i.v. Phenylbutazone was less active ex vivo but did suppress chemotaxis by 23% (P less than 0.05) at 1 h following an i.v. dose of 20 mg/kg. It is suggested that part of the anti-inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment.
Strøm
H
H
Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
Thomsen
M K
MK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003002:Clonixin / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs / Q000097:blood / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D010653:Phenylbutazone / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007975:Leukotriene B4; D009637:Masoprocol; C014558:flunixin meglumine; D010653:Phenylbutazone; D003002:Clonixin; D007213:Indomethacin