In vivo interaction of nonsteroidal anti-inflammatory drugs on the locomotion of neutrophils elicited by acute non-specific inflammations in the rat—Effect of Indomethacin, Ibuprofen and Flurbiprofen

Abstract

The in vivo effects of Flurbiprofen, Ibuprofen and Indomethacin (1.5,6 and 3 mg/kg respectively) were studied on two acute non-specific pleurisies induced by calcium pyrophosphate crystals (CaPP) or decomplemented isologous rat serum (DIRS) in the rat. Drug effects on the exudation phase (pleural exudate volume), leukocyte emigration (number of leukocytes in the fluid) and on random and directed locomotion of elicited neutrophils (PMN) under agarose were investigated. In the CaPP model, Indomethacin, Flurbiprofen and Ibuprofen reduced the pleural exudate volume by approximately 48, 57 and 22% respectively while leukocyte emigration was inhibited 50, 45 and 50% respectively. In the DIRS model Indomethacin and Flurbiprofen reduced the exudate volume by 54 and 52% and leukocyte emigration by 51 and 31% respectively. Ibuprofen administration produced a decrease in exudate volume of only 27%. The three drugs did not alter in vitro locomotion of DIRS-elicited PMN. On the other hand, Flurbiprofen reduced both random and directed locomotion of CaPP-elicited PMN stimulated with peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), isologous rat serum (IRS) or cell-free exudates. Ibuprofen induced a slight increase in random migration of CaPP-elicited PMN while Indomethacin was without effect. None of the three drugs altered the chemotactic activity of inflammatory exudate. These data suggest that therapeutic doses of anti-inflammatory drugs interfere with PMN at inflammatory sites and induce modifications in their movement per se which persist after cell washing.