Effects of ketoprofen and indomethacin on leukocyte migration in two models of pleurisy induced by carrageenan or zymosan-activated serum in rats.
The effect of nonsteroidal anti-inflammatory drugs on the in vivo leukocyte migration is not understood fully. In the present study, the effects of indomethacin and ketoprofen on the intrapleural leukocyte accumulation induced by carrageenan or zymosan-activated serum (ZAS) were investigated. Rats were given indomethacin or ketoprofen p.o. (1, 3 or 9 mg/kg) 1 hr before intrapleural injection of carrageenan (1 mg) or ZAS (0.5 ml). Pleural exudates were harvested 4 hr later. In each model of pleurisies, ketoprofen and indomethacin reduced the volume of exudate and leukocyte count in a dose-dependent manner but ketoprofen was more active than indomethacin. Ketoprofen and indomethacin had no effect on the protein concentration and the total complement activity of the exudates induced by carrageenan or ZAS. The spontaneous and directed migrations of leukocytes elicited by ZAS were unaffected by indomethacin and ketoprofen, whereas those of leukocytes elicited by carrageenan were more inhibited by ketoprofen than by indomethacin. These data demonstrate that ketoprofen is more active than indomethacin in reducing the in vivo leukocyte migration evoked by carrageenan or ZAS and suggest that the main effect of these two drugs is to reduce the increase in vascular permeability. Neutrophil chemotactic responsiveness and generation of chemotactic factors alone cannot explain the anti-inflammatory effect of ketoprofen and indomethacin.
Vannier
E
E
Département de Pharmacologie, UA Centre National de la Recherche Scientifique 595, Hôpital Cochin, Paris, France.
Roch-Arveiller
M
M
Molinie
B
B
Terlain
B
B
Giroud
J P
JP
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D007660:Ketoprofen / Q000494:pharmacology*; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D010998:Pleurisy / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D015054:Zymosan / Q000494:pharmacology
D001798:Blood Proteins; D010666:Phenylpropionates; D002351:Carrageenan; D015054:Zymosan; D007660:Ketoprofen; D007213:Indomethacin