Oxymetazoline Inhibits and Resolves Inflammatory Reactions in Human Neutrophils

Abstract

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 E 2 (PGE 2 ) and anti-inflammatory 15(S)-hydroxy-eicosatetraenoic acid [15(S)-HETE] and depletion of pro-inflammatory leukotriene B 4 (LTB 4 ). 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 LTB 4 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 LTB 4 and 8-isoprostane and inhibited the respiratory burst activity. These findings suggest a switch from the pro-inflammatory eicosanoid class LTB 4 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.

Ultrafine particles affect the balance of endogenous pro- and anti-inflammatory lipid mediators in the lung: in-vitro and in-vivo studies

“…This was due to the oxidative potential of the particles; we found that particles were able to oxidise the amino acid methionine to methionine sulfoxide, and that they showed an ESR signal equivalent to a free radical within the particle core [23]. The pro-resolving mediator LXA 4 also increased during particle incubation, which is in agreement with our recent findings with human neutrophils [35]. LXA 4 is generated via PGE 2 and 15(S)-HETE and represents a stop signal for inflammation to return the inflamed tissue to homeostasis [36].…”

“…Due to the oxidative potential of UFCP [23], arachidonic acid is non-enzymatically oxidized to 8-isoprostane, used as a marker for redox imbalance. Arachidonic acid serves as a substrate for the downstream pathways of COX (cyclooygenase), 15- and 5-LO (15- and 5-lipoxygenase), leading to formation of prostaglandins such as PGE 2 , 15(S)-HETE, leukotrienes such as LTB 4 and to LXA 4 via PGE 2 activated 15-LO [23,26,35]. Because these processes are predominantly located in the nuclear membrane or perinuclear space, these products of these pathways may influence gene expression.…”

Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis

“…In addition to being an a-agonist, oxymetazoline has been shown to have various antioxidative and anti-inflammatory properties. [8][9][10][11][12] Whether any of these effects contributed to our results is unknown. The oxymetazoline was dosed once daily at night.…”

Acute Rhinitis in Children

“…В осно-ве указанного эффекта лежит ингибирование экспрес-сии молекул ICAM-1, обеспечивающих адгезию вирус-ных частиц к клеткам респираторного эпителия [19]. Результаты последующих лабораторных исследований показали, что оксиметазолин обладает также антиокси-дантными и противовоспалительными свойствами [20].…”