Effects of steroidal and non-steroidal antiphlogistic drugs on eicosanoid synthesis in irritated skin:: studies with the isolated perfused bovine udder

Using the isolated perfused bovine udder as an in-vitro model of skin inflammation, the effects of topically administered arachidonic acid on prostaglandin and leukotriene synthesis have been shown previously. In this study, the effects of indometacin (indomethacin) and clobetasol-17-propionate (administered topically) as well as flunixin meglumine and meloxicam (administered via the perfusion fluid) have been studied. Compared with controls, arachidonic acid caused a significant increase in the dermal prostaglandin E-2 (PGE(2)) and peptidoleukotriene (LTC4/D-4/E-4) concentration. Topical treatment with indometacin (1.6 mg cm(-2)) and clobetasol-17-propionate (90 mug cm(-2)), which were administered 60 min before arachidonic acid administration, inhibited the inflammatory reaction. Flunixin meglumine (1 mug mL(-1) perfusion fluid) was administered 30 min after and meloxicam (3 mug mL(-1) perfusion fluid) was administered 60 min before arachidonic acid application. Three hours after arachidonic acid administration, a significant inhibition of PCE2 synthesis was induced by flunixin. In contrast, meloxicam showed only a slight effect. The effect of flunixin was comparable with in-vivo results. It is known from animal studies that anti-inflammatory effects of meloxicam are obvious within up to 6 h after treatment. Therefore, the incomplete effect of meloxicam may be explained pharmacokinetically. In conclusion, the described in-vitro model seems to be suitable for studies of pharmacological effects on eicosanoid synthesis in the skin.