Mehta A K, Gaur S N, Arora N, Singh B P
Allergy and Immunology Section, Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi, India.
Eur Respir J. 2007 Oct;30(4):662-71. doi: 10.1183/09031936.00019307. Epub 2007 Jun 27.
The incidence of asthma has increased the world over, and current therapies for the disease suffer from potential side-effects. This has created an opportunity to develop novel therapeutic approaches. Here, the anti-inflammatory activity of choline was investigated in a mouse model of allergic airway inflammation. Choline (1 mg.kg(-1)) was administered via oral gavage or intranasally before and after ovalbumin (OVA) challenge in sensitised mice. Airway hyperresponsiveness (AHR) to methacholine was measured in the mice by whole-body plethysmography. Type-2 T-helper cell cytokine and leukotriene levels were estimated in bronchoalveolar lavage fluid (BALF) and spleen culture supernatant by ELISA. Eosinophil peroxidase activity was also determined in the BALF supernatant. Choline treatment in sensitised mice before OVA challenge via oral/intranasal routes significantly inhibited eosinophilic airway inflammation and eosinophil peroxidase activity. It also reduced immunoglobulin E and G1 production and inhibited the release of type-2 T-helper cell cytokines and leukotrienes. However, the development of AHR was prevented effectively by intranasal choline treatment. Most importantly, choline treatment after OVA challenge by both routes could reverse established asthmatic conditions in mice by inhibiting AHR, eosinophilic airway inflammation and other inflammatory parameters. This study provides a new therapeutic approach for controlling as well as preventing asthma exacerbations.
全球哮喘发病率呈上升趋势，目前针对该疾病的治疗方法存在潜在副作用。这为开发新的治疗方法创造了契机。在此，研究了胆碱在过敏性气道炎症小鼠模型中的抗炎活性。在致敏小鼠卵清蛋白（OVA）激发前后，通过口服灌胃或鼻内给药给予胆碱（1 mg·kg⁻¹）。通过全身体积描记法测量小鼠对乙酰甲胆碱的气道高反应性（AHR）。通过酶联免疫吸附测定法（ELISA）评估支气管肺泡灌洗液（BALF）和脾细胞培养上清液中2型辅助性T细胞细胞因子和白三烯水平。还测定了BALF上清液中的嗜酸性粒细胞过氧化物酶活性。在OVA激发前通过口服/鼻内途径对致敏小鼠进行胆碱治疗可显著抑制嗜酸性粒细胞性气道炎症和嗜酸性粒细胞过氧化物酶活性。它还降低了免疫球蛋白E和G1的产生，并抑制了2型辅助性T细胞细胞因子和白三烯的释放。然而，鼻内给予胆碱治疗可有效预防AHR的发展。最重要的是，在OVA激发后通过两种途径进行胆碱治疗均可通过抑制AHR、嗜酸性粒细胞性气道炎症和其他炎症参数来逆转小鼠已建立的哮喘状态。本研究为控制和预防哮喘发作提供了一种新的治疗方法。
