Table 1.

Immunomodulatory effects of macrolides on chronic airway diseases.

Effects	Mechanism	Targets	Action
Anti-inflammation	Cell signaling regulation	Interference in the mitogen-activated protein kinase (MAPK) system	Reduce inflammation gene expression and regulate cell growth differentiation
		Modulating the expression of transcription factors (especially NF-kB)
	Interfere with inflammatory cells and cytokines	Decrease in TGF-β1, PDGF, VEGF	Improve chronic airway inflammation and airway remodeling
		Interference with the proliferation of fibroblasts and vascular endothelial cells
		Prevention in the recruitment of eosinophils via inhibition of eosinophil-activated chemokines and IL-5 release
		Improve Th2 inflammation via decrease in IL-4 and IL-13
		Prevention in the recruitment of neutrophils via inhibition of IL-8 and TNF-α
Airway secretion regulation	Cell signaling regulation	Interference with intracellular calcium and chloridion signaling pathway	Decrease in airway water and mucus secretion
		Partial activation of the muscarine receptor
	Interfere with inflammatory cells and cytokines	Inhibition of submucosal mucous adenocytes (goblet cell) via decrease in TNF-α and IL-13
Immunomodulatory-related antimicrobial effects	Inhibition of microbial adhesion	Inhibition of plant hemagglutinin, hemolysin, etc.	Antimicrobial effect below MIC
	Inhibition of virulence factors	Inhibition of exotoxin A, elastase, etc.
	Biofilm inhibition	Inhibition of alginate synthesis in biofilms
	Impair the quorum-sensing system	Blocking expression of signals known as “autoinducers”