Pharmacologic Target of Inhaled Corticosteroids
The pharmacologic target of inhaled corticosteroids is phospholipase A2, which they inhibit as part of their broad anti-inflammatory mechanism of action.
Mechanism of Action
Inhaled corticosteroids exert their therapeutic effects through multiple anti-inflammatory pathways, with phospholipase A2 inhibition being a key mechanism:
Corticosteroids inhibit phospholipase A2, the enzyme responsible for releasing arachidonic acid from cell membrane phospholipids, thereby blocking the production of inflammatory mediators including leukotrienes and prostaglandins 1.
The primary genomic mechanism involves reversing histone acetylation through recruitment of histone deacetylase 2 (HDAC2), which switches off multiple activated inflammatory genes 2.
Through these mechanisms, ICS suppress almost every aspect of the inflammatory process in asthma, affecting multiple inflammatory cells and mediators 3, 4.
Why Not the Other Options
Beta-1 receptors are not the target—these are cardiac receptors, and ICS do not have direct effects on adrenergic receptors. Beta-2 agonists (not corticosteroids) target beta-2 receptors in the airways 1.
Alveolar lymphocytes are affected by ICS but are not the pharmacologic target. While ICS do reduce lymphocytic inflammation in airways, particularly in COPD, this is a downstream effect rather than the primary molecular target 5.
The ciliary elevator system is not directly targeted by ICS. While corticosteroids reduce mucus secretion by inhibiting secretagogue release from macrophages, they do not directly act on ciliary function 1.
Clinical Effects Through Phospholipase A2 Inhibition
By inhibiting phospholipase A2, inhaled corticosteroids achieve multiple therapeutic effects:
Reduction of leukotriene production (LTC4 and LTD4), which decreases bronchoconstriction and vascular permeability 1.
Decreased prostaglandin synthesis, contributing to reduced inflammation and airway hyperresponsiveness 1.
Suppression of inflammatory cell recruitment and activation, leading to control of both early and late-phase allergic responses 4.
Reversal of mucosal edema through vasoconstriction and decreased vascular permeability 6, 1.