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首页> 外文期刊>Clinical and experimental allergy : >Suppressive effects of nitric oxide-releasing prednisolone NCX-1015 on the allergic pleural eosinophil recruitment in rats.
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Suppressive effects of nitric oxide-releasing prednisolone NCX-1015 on the allergic pleural eosinophil recruitment in rats.

机译：一氧化氮释放泼尼松龙NCX-1015对过敏性胸膜嗜酸性粒细胞募集的抑制作用。

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BACKGROUND: The addition of a nitric oxide (NO)-releasing moiety to prednisolone was shown to enhance the anti-inflammatory activity of this glucocorticoid in some experimental conditions, but its effectiveness in the context of eosinophilic inflammation remains to be elucidated. OBJECTIVE: This study compared the anti-inflammatory effect of prednisolone to a NO-releasing derivative of prednisolone, NCX-1015, using a model of allergen-evoked eosinophil recruitment in rats. The efficacy of a NO-donor compound, DETA-NONOate, was also assessed for comparison. METHODS: Wistar rats were actively sensitized with Al(OH)(3) plus ovalbumin and 14 days later challenged with antigen intrapleurally. Treatments were performed locally 1 h before challenge. Cysteinyl-leucotrienes (Cys-LT) and eotaxin were measured by ELISA. RESULTS: Antigen challenge induced an eosinophil infiltration at 12 h, maximal at 24 h. It also caused an increase in the levels of Cys-LTs in the pleural exudate and in the expression of 5-lipoxygenase (5-LO) in infiltrated leucocytes at 6 h, peaking at 12 h and persisting for at least 24 h. Treatment with equimolar doses of prednisolone and NCX-1015 inhibited the late eosinophil infiltration, although the dose required to produce maximal inhibition was about one-tenth that of prednisolone. Cys-LT generation and 5-LO expression were inhibited by NCX-1015 but not by prednisolone. Treatment with prednisolone combined with the NO-donor DETA-NONOate led to a greater inhibition of the eosinophilia and Cys-LT generation as compared with either drug alone. Administration of the steroid receptor antagonist RU 486, 1 h before prednisolone and NCX-1015, abolished the inhibitory effect of the former, under conditions where it only partially affected the latter. CONCLUSIONS: Our findings indicate that NCX-1015 provided a greater anti-inflammatory effect than prednisolone on the allergic eosinophil recruitment in rats, suggesting that NO-releasing steroids can be considered as a promising therapeutic approach to allergic diseases.
机译：背景：在某些实验条件下，向泼尼松龙添加一氧化氮（NO）释放部分可增强该糖皮质激素的抗炎活性，但在嗜酸性粒细胞炎症的背景下其有效性尚待阐明。目的：本研究使用过敏原诱发的嗜酸性粒细胞募集模型，比较了泼尼松龙与泼尼松龙释放NO的衍生物NCX-1015的抗炎作用。还评估了NO供体化合物DETA-NONOate的功效以进行比较。方法：Wistar大鼠用Al（OH）（3）和卵清蛋白主动致敏，并在14天后经胸膜内抗原攻击。攻击前1小时在局部进行治疗。通过ELISA测量半胱氨酸-亮氨酸（Cys-LT）和嗜酸性粒细胞趋化因子。结果：抗原攻击在12 h诱导了嗜酸性粒细胞浸润，在24 h达到最大浸润。它也引起胸膜渗出液中Cys-LTs水平的增加以及6h浸润白细胞中5-脂氧合酶（5-LO）的表达增加，在12h达到峰值，并持续至少24h。用等摩尔剂量的泼尼松龙和NCX-1015处理可抑制晚期嗜酸性粒细胞浸润，尽管产生最大抑制作用所需的剂量约为泼尼松龙的十分之一。 Cyx-LT的产生和5-LO表达被NCX-1015抑制，但泼尼松龙未抑制。与单独使用任一药物相比，泼尼松龙与NO供体DETA-NONOate联合治疗导致对嗜酸性粒细胞增多和Cys-LT产生的抑制作用更大。在泼尼松龙和NCX-1015之前1小时给予类固醇受体拮抗剂RU 486，在仅部分影响后者的情况下，取消了前者的抑制作用。结论：我们的研究结果表明，NCX-1015对泼尼松龙在大鼠过敏性嗜酸性粒细胞募集方面提供了比泼尼松龙更大的抗炎作用，这表明释放NO的类固醇可被视为治疗过敏性疾病的一种有前途的治疗方法。

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