Topical arachidonic acid: a model for screening anti-inflammatory agents

Products of arachidonic acid metabolism, prostaglandins and leukotrienes, play an important role in ocular inflammation. In this study, we investigated the efficacies of the cyclo-oxygenase inhibitors (aspirin, indomethacin, and piroxicam) and the lipoxygenase inhibitors (N-hydroxy-arachidonamide (AH) and phenidone) in reducing ocular inflammation induced by arachidonic acid. Administering arachidonic acid topically (0.50% for rabbits and 0.25% for humans) produced a simple model for evaluating the effects of inhibitors on prostaglandins. In rabbits, aspirin, piroxicam and indomethacin all blocked lid closure and chemosis significantly. In humans, aspirin and indomethacin significantly blocked arachidonic acid-induced conjunctival injection. Neither AH nor phenidone blocked any of the signs of ocular inflammation in rabbits or humans. Further testing of phenidone in the presence of the calcium ionophore, ionomycin, also proved negative. Species specificity in arachidonic acid metabolism may account for the different results in humans and rabbits. This model may be a useful tool for comparing the relative efficacies of topical cyclo-oxygenase inhibitors in treating ocular problems.