Corticosteroid-insensitive asthma: molecular mechanisms.
Corticosteroids are the most potent anti-inflammatory agents used to treat chronic inflammatory diseases such as bronchial asthma. However, there are a small number (<5%) of asthmatic patients who do not respond well, or at all, to corticosteroid therapy - the corticosteroid-resistant and corticosteroid-dependent patients. Although this phenomenon is relatively uncommon, it poses a difficult therapeutic problem because few alternative therapies are available and these patients account for >50% of the health care costs of asthma. If the mechanisms for corticosteroid insensitivity are understood they may, in turn, provide insight into the key mechanism of corticosteroid action and allow a rational way to treat these individuals whose disease tends to be severe. Corticosteroid insensitivity is not limited to asthma and is a feature of other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Thus, elucidation of the cause for the relative lack of corticosteroid response in this subgroup of asthmatic individuals may have important implications for other diseases.
Adcock
I M
IM
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK. ian.adcock@imperial.ac.uk
Lane
S J
SJ
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D002648:Child; D018432:Drug Resistance, Multiple; D015870:Gene Expression; D006801:Humans; D007378:Interleukins / Q000276:immunology; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D017211:Treatment Failure
D000893:Anti-Inflammatory Agents; D007378:Interleukins; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1