Self-limiting anti-inflammatory actions of glucocorticoids in asthma

糖皮质激素在哮喘中的自限性抗炎作用

• 批准号: nhmrc : 145693
• 负责人: Prof Alastair Stewart
• 金额: $ 25.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/self-limiting-anti-glucocorticoids-asthma/76775
• 关键词: Self; limiting; anti; inflammatory; actions

Asthma is a disease characterised by excessive narrowing of the airway tubes resulting in difficulty exhaling air from the lungs. Symptoms of asthma include coughing, wheezing, shortness of breath and difficulty in breathing. Asthma affects almost 1 in 5 Australians and is especially prevelant in children. One in every three Australians will suffer from symptoms of asthma at some time in their life and despite current therapy, asthma is responsible for the deaths of more than 700 Australians every year. Airway tubes of asthmatics have more and larger contractile muscle cells lining the tubes. This increase in muscle mass results from chemicals that are released from white blood cells that migrate into the airway tubes during and after asthma attacks. This thickening slows airflow through the airway tubes because the muscle mass bulges into the holes of the tubes and when the muscle shortens the total diameter of the tubes decrease. We have recently shown that steroids used by asthmatics to treat the white blood cell contribution to the disease can reduce the growth of airway muscle. However, when the muscle has been pretreated with factors that are present in the inflamed airway, the anti-growth effects of steroids are prevented. This effect of the steroids is due to reduced production of a substance called prostaglandin E2 which can also reduce the growth of muscle. Thus, whilst steroids may help in treating some of the symptoms of asthma, they may be suboptimal in the treatment of muscle thickening and other aspects of the disease which involve cell division and multiplication. Our specific question in the next phase of this research is whether steroid inhibition of the release of prostaglandins compromises the useful actions of steroids on the growth of the airway tubes. The findings of this proposed study will provide new information on the role of steroids in asthma and may lead to better therapeutic strategies for the treatment of severe asthma.

哮喘是一种疾病，其特征是气道过度狭窄，导致难以从肺部呼出空气。哮喘的症状包括咳嗽、喘鸣、呼吸短促和呼吸困难。哮喘影响近五分之一的澳大利亚人，尤其是儿童。每三个澳大利亚人中就有一个人会在一生中的某个时候患上哮喘症状，尽管目前有治疗方法，但哮喘每年仍导致700多名澳大利亚人死亡。哮喘患者的气道有更多、更大的收缩肌细胞排列在管道上。这种肌肉质量的增加是由于哮喘发作期间和之后从白色血细胞中释放的化学物质迁移到气道中。这种增厚减缓了通过气道导管的气流，因为肌肉块凸出到导管的孔中，并且当肌肉缩短时，导管的总直径减小。我们最近发现，哮喘患者使用类固醇来治疗白色血细胞对疾病的贡献，可以减少气道肌肉的生长。然而，当肌肉已经用存在于发炎气道中的因子预处理时，类固醇的抗生长作用被阻止。类固醇的这种作用是由于减少了一种叫做前列腺素E2的物质的产生，这种物质也可以减少肌肉的生长。因此，虽然类固醇可以帮助治疗哮喘的一些症状，但它们在治疗肌肉增厚和涉及细胞分裂和增殖的疾病的其他方面可能是次优的。我们在下一阶段研究的具体问题是，类固醇抑制肾上腺素释放是否会损害类固醇对气道生长的有用作用。这项研究的结果将为类固醇在哮喘中的作用提供新的信息，并可能为治疗严重哮喘提供更好的治疗策略。