*Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Clin Sci (Lond). 2014 Jun;126(11):805-14. doi: 10.1042/CS20130623.
Endogenous mediators, such as RvE1 (resolvin E1), promote resolution of an inflammatory response and have potential as novel therapeutic agents. In the present study, we investigated the activity of RvE1 in a model of an acute exacerbation of chronic allergic asthma in mice. Animals sensitized to OVA (ovalbumin) received controlled low-level challenge with aerosolized antigen for 4 weeks, followed by a single moderate-level challenge to simulate an allergen-induced exacerbation of asthmatic inflammation. Induction of an exacerbation was associated with rapid recruitment of neutrophils, lymphocytes and eosinophils, together with increased levels of Th2 and pro-inflammatory cytokines. When administered before the final moderate-level challenge, RvE1 had only a modest effect on airway inflammation. To assess its effects when administered after induction of an exacerbation, we first characterized the cellular and molecular events associated with spontaneous resolution of airway inflammation over the following 96 h. Subsequently, we showed that administration of RvE1 at 2 and 8 h after the final challenge accelerated this process significantly. Specifically, RvE1 promoted a decline in the number of inflammatory cells, concentration of cytokines in lavage fluid and expression of mRNA for cytokines by macrophages, confirming its pro-resolution activity. In vitro, RvE1 had no apparent effect on lymphocytes, but suppressed significantly cytokine production by pulmonary macrophages, with evidence of down-regulation of the nuclear translocation of NF-κB (nuclear factor κB) p65 in these cells. The present study provides novel evidence that RvE1 can facilitate resolution of airway inflammation in a clinically relevant model of an acute exacerbation of asthma, possibly via its effects on activated pulmonary macrophages.
内源性介质，如 RvE1（消退素 E1），可促进炎症反应的消退，并具有作为新型治疗剂的潜力。在本研究中，我们研究了 RvE1 在慢性变应性哮喘急性加重小鼠模型中的活性。对 OVA（卵清蛋白）致敏的动物接受了为期 4 周的雾化抗原的低水平控制挑战，随后进行了单次中等水平的挑战以模拟变应原诱导的哮喘炎症加重。加重的诱导与中性粒细胞、淋巴细胞和嗜酸性粒细胞的快速募集有关，同时 Th2 和促炎细胞因子的水平也增加了。当在最后一次中度挑战之前给予时，RvE1 对气道炎症仅有适度的影响。为了评估在加重诱导后给予时的效果，我们首先描述了与气道炎症自发消退相关的细胞和分子事件，持续了接下来的 96 小时。随后，我们表明在最后一次挑战后的 2 小时和 8 小时给予 RvE1 可显著加速这一过程。具体而言，RvE1 促进了炎症细胞数量、灌洗液中细胞因子浓度和巨噬细胞中细胞因子 mRNA 表达的下降，证实了其促消退活性。在体外，RvE1 对淋巴细胞没有明显作用，但显著抑制了肺巨噬细胞细胞因子的产生，并且这些细胞中 NF-κB（核因子 κB）p65 的核易位也明显下调。本研究提供了新的证据，表明 RvE1 可以促进临床相关的哮喘急性加重模型中的气道炎症消退，可能是通过其对活化的肺巨噬细胞的作用。
