Directional movement of cells in vivo and in vitro under the influence of 5-lipoxygenase inhibitors

Abstract

Five inhibitors of 5-lipoxygenase activity [phenidone, nordihydroguaiaretic acid (NDGA), BW755c, nafazatrom and the methyl ester of caffeic acid] have been compared with the cyclo-oxygenase inhibitor indomethacin as inhibitors of aggregation and chemotaxis by guinea-pig polymorphonuclear leukocytes. The results suggest that neither 5-lipoxygenase nor cyclo-oxygenase products are of significance in these in vitro assays. However, all of these compounds, with the exception of BW755c, significantly inhibited cell accumulation in an acute inflammatory model. These results cast doubt on the central importance of any individual arachidonic acid metabolite in the development of inflammation in vivo.