Oxymetazoline Inhibits and Resolves Inflammatory Reactions in Human Neutrophils

The nasal decongestant oxymetazoline (OMZ) exhibits anti-oxidative and anti-inflammatory 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 E-2 (PGE(2)) and anti-inflammatory 15(S)hydroxy-eicosatetraenoic acid [15(S)-HETE] and depletion of pro-inflammatory leukotriene B-4 (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 PGE(2), 15(S)-HETE, and LXA(4). 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 PGE(2), 15(s)-HETE, and LXA(4), 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 LXA(4). Since LXA(4) is most relevant in returning inflamed tissue to homeostasis, OMZ is postulated to terminate rhinitis-related inflammation, thus contributing to shortening of disease duration.