Abstract

ALVARADO-GONZALEZ, Alcibey  and  ARCE-JIMENEZ, Isabel. Glucocorticoid action and resistance mechanisms in asthma and chronic obstructive pulmonary disease. Acta méd. costarric [online]. 2013, vol.55, n.4, pp.162-168. ISSN 0001-6002.

Bronchial asthma and chronic obstructive pulmonary disease are two major health problems whose incidence is increasing. Both are a widely recognized cause of morbidity and mortality. Glucocorticoids have been identified as the drug of choice for the treatment of chronic inflammatory and immune diseases, such as bronchial asthma and chronic obstructive pulmonary disease. The well-known efficiency of these drugs is attributable to their suppression of inflammation in several molecular pathways. Its main action at therapeutic doses is due to trans-repression of activated inflammatory genes, through the recruitment and action of the enzyme histone desacetylase-2 and the subsequent remodeling of chromatin. At higher concentrations, glucocorticoids act as trans-activators, acetylating histones and stimulating the transcription of anti-inflammatory genes. Eventually, this mechanism could be involved in the activation of genes related to side effects. Post-transcriptional effects that modulate the stability of mRNA have been proved. Nevertheless, decreased glucocorticoid responsiveness is found in patients with severe asthma and asthmatics who smoke, as well as in all patients with chronic obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid resistance have been identified. Alternative anti-inflammatory treatments that may allow for the control of these patients’ symptoms and drugs that may reverse molecular mechanisms of resistance are being investigated. Unfortunately, these therapies might be too specific to be effective, as is the case of dissociated glucocorticoids, where it has been difficult to dissociate anti-inflammatory effects from adverse effects.

Keywords : Asthma; chronic obstructive pulmonary disease; drug resistance; glucocorticoids.

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