Oxymetazoline Inhibits and Resolves Inflammatory Reactions in Human Neutrophils

Abstract

.The nasal decongestant oxymetazoline (OMZ) exhibits anti-oxidative and antiinflammatory properties (I. Beck-Speier et al., J Pharmacol Exp Ther. 2006;316:842–851). In a follow up study, we hypothesized that OMZ generates pro-resolving lipoxins being paralleled by production of immune-modulating prostaglandin E2 (PGE2) and anti-inflammatory 15(S)-hydroxy-eicosatetraenoic acid [15(S)-HETE] and depletion of pro-inflammatory leukotriene B4 (LTB4). Human neutrophils (PMN) were chosen as the cellular system. The effect of OMZ on these parameters as well as on respiratory burst activity and oxidative stress marker 8-isprostane was analyzed in unstimulated and co-stimulated PMN by ultrafine carbon particles (UCP) or opsonized zymosan (OZ), respectively. In unstimulated cells, OMZ induced formation of PGE2, 15(S)-HETE, and LXA4. The levels of LTB4 and 8-isoprostane were not affected, whereas respiratory burst activity was drastically inhibited. In UCP- and OZ-stimulated control cells, all parameters were elevated. Here, OMZ maintained the increased levels of PGE2, 15(S)-HETE, and LXA4, but substantially suppressed levels of LTB4 and 8-isoprostane and inhibited the respiratory burst activity. These findings suggest a switch from the pro-inflammatory eicosanoid class LTB4 to the pro-resolving LXA4. Since LXA4 is most relevant in returning inflamed tissue to homeostasis, OMZ is postulated to terminate rhinitis-related inflammation, thus contributing to shortening of disease duration.