Mechanisms of Action of Glucocorticoids in Obstructive Pulmonary Diseases

Abstract

Glucocorticoids are the most effective anti-inflammatory drugs for asthma and some groups of COPD patients. Glucocorticoids suppress inflammation by several mechanisms. Its principal action at therapeutic doses is due to trans-repression of activated inflammatory genes, by the recruitment of the enzyme histone desacetylase-2 and the subsequent remodeling of chromatin. At higher concentration, 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. This mechanism of action is known as genomic. In the last decades, a mechanism of local action with the use of glucocorticoids involving an interaction between glucocorticoids and noradrenaline has been described, through a membrane receptor in the smooth muscle of the blood vessels that reduces hyper-perfusion and mucosal edema. This mechanism is known as non-genomic. This chapter discusses and compares both mechanisms by establishing similarities and differences between the two.