The inactivation of the polymorphonuclear leukocyte by non-steroidal anti-inflammatory drugs.
When human neutrophils (PMNs) are activated by appropriate stimuli, they aggregate, generate superoxide anion (O2-) and secrete lysosomal enzymes. Pre-incubation of PMNs in vitro with the cyclo-oxygenase (COx) inhibitor piroxicam (50 microM) before stimulation with the chemotactic peptide f-met-leu-phe (FMLP, 10(-7)M) inhibited all of these responses. The COx inhibitor ibuprofen inhibited FMLP-induced aggregation and lysozyme secretion, leaving O2- generation unaffected. Binding of 3H-FMLP was inhibited by piroxicam. When the plant lectin concanavalin A (Con-A, 30 micrograms/ml) or the tumor promoter phorbol myristate acetate (PMA, 50 micrograms/ml) was used as a stimulus, ibuprofen had no effect on PMN response, while piroxicam inhibited only O2- generation. To determine whether such inhibition might also occur in vivo, we tested neutrophil aggregation and O2- generation in response to FMLP in 26 normal subjects. These subjects were then administered therapeutic doses of piroxicam (20 mg/day), ibuprofen (2400 mg/day) or indomethacin (100 mg/day), and neutrophil functions were retested after 3 days. Piroxicam inhibited FMLP-induced aggregation by 31% (5.2 cm2/min versus 3.6 cm2/min, P less than 0.004) and O2- generation by 35% (15.8 nmol cytochrome c reduced versus 10.2 nmol, P less than 0.002). Ibuprofen inhibited FMLP-induced aggregation by 44% (5.2 versus 3.0, P less than 0.03) but had no effect on O2- production. Indomethacin inhibited FMLP-induced aggregation (6.4 versus 2.9, P less than 0.01) but had no effect on O2- generation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology; D008247:Lysosomes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D013481:Superoxides / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D013481:Superoxides