Self-limiting anti-inflammatory actions of glucocorticoids in asthma

点击翻译按钮获取中文摘要

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.