What is the relationship between corticosteroids and eosinophil levels?

The Relationship Between Corticosteroids and Eosinophils

Corticosteroids significantly reduce eosinophil counts in both blood and tissues through multiple mechanisms including induction of apoptosis, down-regulation of chemotactic factors, and inhibition of proinflammatory mediators. 1

Mechanisms of Action

Corticosteroids affect eosinophils through several key mechanisms:

1. Direct effects on eosinophil survival:

   • Induce eosinophil apoptosis (programmed cell death) 2
   • Inhibit anti-apoptotic cytokines (IL-3, IL-5, GM-CSF, IL-9, IL-13, IL-15) that normally prolong eosinophil survival 2

2. Reduction of eosinophil recruitment and activation:

   • Down-regulate chemotactic factors that attract eosinophils to tissues 1
   • Inhibit proinflammatory mediators that activate eosinophils 3

3. Enhanced clearance of apoptotic eosinophils:

   • Promote phagocytosis of apoptotic eosinophils by macrophages and bronchial epithelial cells 2
   • Facilitate receptor-mediated recognition and engulfment of dead eosinophils 2

Clinical Effects on Eosinophil Counts

Systemic Corticosteroids

• Produce rapid and profound reductions in blood eosinophil counts
• Studies show a 30-36% reduction in blood eosinophil counts within one month of systemic corticosteroid initiation 4
• In patients with initial counts ≥400 cells/μL, mean reduction of 290 cells/μL (36% decrease) observed 4

Inhaled Corticosteroids (ICS)

• Cause significant dose-dependent reductions in blood eosinophil counts
• Increasing from medium to high-dose ICS results in median reduction from 560 to 320 cells/μL 5
• Effects may be seen as early as 6 hours after administration in asthma patients 1

Clinical Applications

Eosinophilic Airway Diseases

• In asthma and non-asthmatic eosinophilic bronchitis (NAEB), inhaled corticosteroids are first-line treatment 3
• The presence of eosinophilic airway inflammation predicts a favorable response to corticosteroid therapy 3
• For NAEB, inhaled corticosteroids significantly improve symptoms and reduce sputum eosinophil counts 3

Eosinophilic Esophagitis (EoE)

• Both systemic and topical corticosteroids effectively reduce esophageal eosinophilia 3
• Systemic corticosteroids (prednisone 1-2 mg/kg/day) improve symptoms within 7 days and esophageal histology within 4 weeks 3
• Topical (swallowed) corticosteroids are preferred due to fewer systemic side effects 3

Hypereosinophilic Syndromes

• Corticosteroids remain the mainstay of treatment for most patients with hypereosinophilic syndromes 6

Monitoring Response

• A halving or doubling of sputum eosinophil count is considered clinically significant 1
• Blood eosinophil suppression after corticosteroid initiation may predict clinical response:
  • In COPD patients, eosinophil suppression ≥200 cells/μL after ICS initiation predicted better outcomes 7
  • Conversely, patients with increased eosinophil counts after ICS had worse outcomes 7

Important Clinical Considerations

• Persistent effects after discontinuation: Blood eosinophil counts may remain suppressed for several weeks after corticosteroid discontinuation 4
• Dose-dependent effects: "Normal values" of blood eosinophils in patients with asthma need to be interpreted in the context of the individual's ICS dose 5
• Biomarker implications: ICS treatment may reduce blood eosinophil counts below thresholds required for biologic therapy eligibility 5
• Corticosteroid resistance: A small proportion of patients may have defects in caspase-induced eosinophil apoptosis, contributing to corticosteroid insensitivity 2

Pharmacological Considerations

Fluticasone propionate, a potent synthetic corticosteroid, exemplifies how these medications affect eosinophils:

• Decreases nasal mucosal eosinophils in 66% of patients (vs. 35% for placebo) 8
• Has high glucocorticoid receptor potency (3-5 times more potent than dexamethasone) 8
• Works through multiple anti-inflammatory pathways affecting eosinophils and other inflammatory cells 8

Understanding this relationship between corticosteroids and eosinophils has led to the development of targeted therapies like mepolizumab, which specifically targets IL-5 to reduce eosinophilic inflammation in severe asthma 9.