Effect of topically applied cyclosporin A on arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation in mouse ear.
Topical cyclosporin A (CsA) was compared with dexamethasone, indomethacin and phenidone in edema, increases in vascular permeability, eicosanoids and cell-influx induced by arachidonic acid (AA) and tetradecanoylphorbol acetate (TPA) in mouse ears. CsA ED(50) on AA-edema (7.7 micrograms/ear) was similar to dexamethasone and lower than indomethacin and phenidone. CsA ED(50) in TPA edema (21 micrograms/ear) was higher than dexamethasone and lower than indomethacin or phenidone. All drugs equally reduce the AA-induced increase in vascular permeability, but CsA and dexamethasone had more activity on TPA. AA-increase in vascular 6-keto-PGF1 alpha was reduced by dexamethasone, indomethacin and phenidone but not by CsA; only phenidone reduced LTB4. TPA-increase in 6-keto-PGF1 alpha was reduced by CsA and indomethacin while CsA, dexamethasone and phenidone decreased LTB4. CsA, indomethacin and phenidone, but not dexamethasone, suppressed AA-neutrophil influx. In TPA-ears all drugs produced similar reduction in neutrophil influx. CsA was shown to be a good topical anti-inflammatory drug.
Puigneró
V
V
Unitat de Fisiologia, Facultat de Farmàcia Universitat de Barcelona, Spain.
Queralt
J
J
D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000633:toxicity; D002199:Capillary Permeability / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016572:Cyclosporine / Q000008:administration & dosage*; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis; D005938:Glucocorticoids / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D016718:Arachidonic Acid; D003907:Dexamethasone; D016572:Cyclosporine; D009195:Peroxidase; D000118:Acetylglucosaminidase; C015429:phenidone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin