Table 7

Potential effects of macrolides in COPD

Macrolide actionProposed mechanism of action in COPD
Antimicrobial
  • Direct antimicrobial action against bacteria commonly associated with exacerbations in COPD (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Chlamydia pneumoniae and Mycoplasma pneumoniae)

  • Indirect antimicrobial action through inhibition of bacterial quorum sensing

Reduce airway inflammation
  • Reduce adhesion molecule expression by epithelial and endothelial cells (ICAM-1, V-CAM-1)

  • Modulates pro-inflammatory cytokine release (IL-1, IL-6, IL-8, TNF∝)

  • Inhibits signalling pathways (AP-1 and NK-kB transcription factors)

  • Influences Toll-like receptor expression and activity

Mucus production
  • Antibacterial action inhibits bacterial induced MUC5AC production

  • Downregulates protein secretion and expression of MUC5AC mRNA

  • Inhibits chloride secretion

Innate immunity
  • Macrophages: enhance phagocytosis and monocyte–macrophage differentiation and reduces metalloproteinase production

  • Neutrophils: reduce chemotactic response, elastolytic activity and tissue accumulation. Inhibits superoxide anion production. Enhances superoxide dismutase activity

Adaptive immunity
  • Lymphocytes: inhibit pro-inflammatory cytokine production and increases apoptosis

  • Dendritic cells: modulate pro-inflammatory cytokine production

Prokinetic in GI tract
  • Reduce gastro-oesophageal reflux and microaspiration leading to airway inflammation

  • This table 7 adapted from Blasi et al.81