Inhibition of some human neutrophil functions by the cyclooxygenase inhibitor ketorolac tromethamine.
Ketorolac tromethamine, a new nonsteroidal anti-inflammatory agent of the pyrrolo-pyrrole group, was assayed for inhibitory effects on polymorphonuclear leukocytes (PMN) in a variety of systems. Ketorolac inhibited PMN superoxide anion generation, lysozyme release, myeloperoxidase release, adherence to plastic surfaces, and chemotaxis in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) in a dose-dependent manner. Ketorolac also inhibited phorbol myristate acetate-stimulated adherence of PMN to bovine pulmonary artery endothelial cells. The drug inhibited lysozyme and myeloperoxidase release by PMN in response to C5a but failed to inhibit C5a stimulation of PMN in any of the other assays. Levels of ketorolac required to inhibit PMN function in most systems were in the range of 0.2 to 1.0 mg/ml, but chemotaxis to fMLP was inhibited by concentrations of ketorolac as low as 1 microgram/ml. Ketorolac, currently the only nonsteroidal anti-inflammatory drug available in a parenteral form may have therapeutic usefulness in a variety of conditions thought to be mediated in part by PMN, including sepsis.
Hyers
T M
TM
Division of Pulmonology and Pulmonary Occupational Medicine, St. Louis University School of Medicine, Missouri.
Tricomi
S M
SM
Liao
J J
JJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004338:Drug Combinations; D006801:Humans; D020911:Ketorolac Tromethamine; D007700:Kinetics; D007975:Leukotriene B4 / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014325:Tromethamine / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D014325:Tromethamine; D013481:Superoxides; D007975:Leukotriene B4; D020911:Ketorolac Tromethamine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D014046:Tolmetin