Arachidonic acid metabolism in the murine eosinophil. III. Effect of nonsteroid anti-inflammatory drugs on lymphokine-directed eosinophil migration in vivo.
In vitro studies of murine eosinophils indicated that lymphokine-stimulated metabolism of arachidonic acid by a lipoxygenase pathway was required for a migration response. In this study we tested the effects of drugs that affect arachidonic acid metabolism on lymphokine-dependent eosinophil accumulation in vivo by the use of 111In-labeled eosinophils. Indomethacin at different dosages either stimulated (1 mg/kg) or partially inhibited (5 to 25 mg/kg) eosinophil accumulation. Aspirin had no significant effects in doses up to 50 mg/kg. BW755C, a drug that inhibits both cyclooxygenase and lipoxygenase, dramatically inhibited eosinophil accumulation at 25 to 125 mg/kg. Pretreatment in vitro of 111In-labeled eosinophils with some drugs known to inhibit lipoxygenase reduced their subsequent accumulation at a lymphokine-injected site in vivo, but the high concentrations required for inhibition suggested that the effects of the drugs were at least partially reversible. Pretreatment with indomethacin did not inhibit the ability of 111In-labeled eosinophils to accumulate at the site of lymphokine injection in vivo. It may be anticipated from these results that drugs inhibiting lipoxygenase will have critical effects on manifestations of immunologic reactions that recruit eosinophils.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002464:Cell Migration Inhibition; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008222:Lymphokines / Q000008:administration & dosage; D008297:Male; D009637:Masoprocol; D051379:Mice; D008808:Mice, Inbred CBA; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D002396:Catechols; D008222:Lymphokines; D011720:Pyrazoles; C022227:eosinophil stimulating promoter; D015117:5,8,11,14-Eicosatetraynoic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D001241:Aspirin; D007213:Indomethacin