TY - JOUR T1 - Oxymetazoline Inhibits Proinflammatory Reactions: Effect on Arachidonic Acid-Derived Metabolites JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 843 LP - 851 DO - 10.1124/jpet.105.093278 VL - 316 IS - 2 AU - Ingrid Beck-Speier AU - Niru Dayal AU - Erwin Karg AU - Konrad L. Maier AU - Gabriele Schumann AU - Manuela Semmler AU - Stephan M. Koelsch Y1 - 2006/02/01 UR - http://jpet.aspetjournals.org/content/316/2/843.abstract N2 - The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning inflammatory and oxidative stress-dependent reactions. The ability of oxymetazoline to model pro- and anti-inflammatory and oxidative stress responses was evaluated in cell-free systems, including 5-lipoxygenase (5-LO) as proinflammatory, 15-lipoxygenase (15-LO) as anti-inflammatory enzymes, and oxidation of methionine by agglomerates of ultrafine carbon particles (UCPs), indicating oxidative stress. In a cellular approach using canine alveolar macrophages (AMs), the impact of oxymetazoline on phospholipase A2 (PLA2) activity, respiratory burst and synthesis of prostaglandin E2 (PGE2), 15(S)-hydroxy-eicosatetraenoic acid (15-HETE), leukotriene B4 (LTB4), and 8-isoprostane was measured in the absence and presence of UCP or opsonized zymosan as particulate stimulants. In cell-free systems, oxymetazoline (0.4-1 mM) inhibited 5-LO but not 15-LO activity and did not alter UCP-induced oxidation of methionine. In AMs, oxymetazoline induced PLA2 activity and 15-HETE at 1 mM, enhanced PGE2 at 0.1 mM, strongly inhibited LTB4 and respiratory burst at 0.4/0.1 mM (p < 0.05), but did not affect 8-isoprostane formation. In contrast, oxymetazoline did not alter UCP-induced PLA2 activity and PGE2 and 15-HETE formation in AMs but inhibited UCP-induced LTB4 formation and respiratory burst at 0.1 mM and 8-isoprostane formation at 0.001 mM (p < 0.05). In opsonized zymosan-stimulated AMs, oxymetazoline inhibited LTB4 formation and respiratory burst at 0.1 mM (p < 0.05). In conclusion, in canine AMs, oxymetazoline suppressed proinflammatory reactions including 5-LO activity, LTB4 formation, and respiratory burst and prevented particle-induced oxidative stress, whereas PLA2 activity and synthesis of immune-modulating PGE2 and 15-HETE were not affected. The American Society for Pharmacology and Experimental Therapeutics ER -