How Do Corticosteroids Work in Asthma?

Clinical Principles

Asthma is the most common chronic disease in westernized countries.

Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants.

This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness.

Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms.

Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular mechanisms involved are now being elucidated.

Physiologic Principles

Inflammation in asthma is characterized by the increased expression of multiple inflammatory genes, including those encoding for cytokines, chemokines, adhesion molecules, and inflammatory enzymes and receptors.

Increased expression of inflammatory genes is regulated by proinflammatory transcription factors, such as nuclear factor-κB and activator protein-1. These bind to and activate coactivator molecules, which then acetylate core histones and switch on gene transcription.

Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways by reversing histone acetylation of the activated inflammatory genes.

This mechanism acts by binding of the activated glucocorticoid receptors to coactivators and recruitment of histone deacetylases to the activated transcription complex.

Understanding how corticosteroids work in patients with asthma may help in designing novel corticosteroids with less systemic effects, as well as novel anti-inflammatory approaches.

These molecular mechanisms of action of …