Received for publication July 27, 2005.
Revised October 7, 2005.
Accepted for publication October 11, 2005.

Oxymetazoline inhibits pro-inflammatory reactions: Effect on arachidonic acid-derived metabolites

Abstract

The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning inflammatory and oxidative stress-dependent reactions. Oxymetazoline`s ability to model pro-, anti-inflammatory and oxidative stress responses was evaluated in cell-free systems including 5-lipoxygenase (5-LO) as pro-inflammatory, 15-lipoxygenase (15-LO) as anti-inflammatory enzymes and oxidation of methionine by agglomerates of ultrafine carbon particles (UCP) 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-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 mM to 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 mM/0.1 mM (p<0.05) but did not affect 8-isoprostane formation. In contrast, oxymetazoline did not alter UCP-induced PLA₂ activity, 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 pro-inflammatory 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.

Key words: alveolar macrophages, leukotrienes, lipoxygenases, oxidative stress, oxymetazoline, prostaglandins

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