Department of Applied Therapeutics, Kuwait University, Kuwait.
Eur J Pharmacol. 2010 Apr 25;632(1-3):73-8. doi: 10.1016/j.ejphar.2009.12.004. Epub 2009 Dec 16.
Asthma is a chronic inflammatory disease of the airways. The treatment of asthma is far from optimal and hence the need for novel therapeutic agents exists. The purpose of this study was to assess the anti-asthma effects of an enaminone, E121, and also its effects on human peripheral blood mononuclear cell proliferation and cytokine release. The effects of E121 were assessed in an ovalbumin-induced model of airway inflammation and airway hyperresponsiveness. In addition, the effects of E121 on phytohemagglutinin (PHA), anti-CD3 monoclonal antibody and lipopolysaccharide (LPS)-induced human peripheral blood mononuclear cell proliferation and cytokine release, respectively, were assessed. Treatment of mice with E121 significantly decreased the ovalbumin-induced increase in airway total cell influx and eosinophil infiltration and this was associated with an inhibition of ovalbumin-induced airway hyperresponsiveness. Moreover, E121 reduced PHA and anti-CD3-induced human peripheral blood mononuclear cell proliferation in vitro. E121 also inhibited PHA, anti-CD3 monoclonal antibody and LPS-induced cytokine release from human peripheral blood mononuclear cell cultures. These findings indicate that E121 exhibits anti-inflammatory and immunosuppressive activities.
哮喘是一种气道的慢性炎症性疾病。哮喘的治疗远非理想，因此需要新型治疗药物。本研究旨在评估烯胺酮 E121 的抗哮喘作用及其对人外周血单个核细胞增殖和细胞因子释放的影响。E121 的作用在卵清蛋白诱导的气道炎症和气道高反应性模型中进行了评估。此外，还分别评估了 E121 对植物血球凝集素（PHA）、抗 CD3 单克隆抗体和脂多糖（LPS）诱导的人外周血单个核细胞增殖和细胞因子释放的影响。用 E121 治疗小鼠可显著降低卵清蛋白诱导的气道总细胞流入和嗜酸性粒细胞浸润的增加，这与抑制卵清蛋白诱导的气道高反应性有关。此外，E121 还可抑制体外 PHA 和抗 CD3 诱导的人外周血单个核细胞增殖。E121 还抑制 PHA、抗 CD3 单克隆抗体和 LPS 诱导的人外周血单个核细胞培养物中细胞因子的释放。这些发现表明，E121 具有抗炎和免疫抑制活性。
