Modulation of leukotriene metabolism from human polymorphonuclear granulocytes by bifonazole

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Abstract
The influence of bifonazole and other azoles on the leukotriene-metabolism of human neutrophil granulocytes (PMN) was investigated. The cells were stimulated with the Ca-ionophore A23187 over 15 minutes in the presence of the azoles. Subsequently the supernatants were analyzed for their leukotriene content by reversed-phase HPLC. In order to confirm that the observed effects are not due to cytotoxic phenomena tests were performed to evaluate the viability of the granulocytes. The chemotactic active leukotriene B4 (LTB4) and its inactive omega-metabolites were detected and quantified by HPLC analysis. The results clearly demonstrated that bifonazole inhibited the omega-oxidation already at concentrations as low as 0.5 microgram ml-1. As a consequence the LTB4-level became elevated. At concentrations up to 64 micrograms ml-1 bifonazole totally blocked the formation of leukotrienes in human granulocytes. Identical experiments were performed with other azoles and with various anti-inflammatory drugs just to have a comparison with bifonazole. It is evident that bifonazole in addition to its well known antimycotic action shows a unique modulation of the leukotriene-metabolism, which is important for its anti-inflammatory potency.