Dapsone inhibits IL-8 secretion from human bronchial epithelial cells stimulated with lipopolysaccharide and resolves airway inflammation in the ferret

Chest. 2011 Oct;140(4):980-990. doi: 10.1378/chest.10-2908. Epub 2011 Mar 24.


Background: IL-8 is an important activator and chemoattractant for neutrophils that is produced by normal human bronchial epithelial (NHBE) cells through mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 pathways. Dapsone, a synthetic sulfone, is widely used to treat chronic neutrophil dermatoses. We investigated the effects of dapsone on polarized IL-8 secretion from lipopolysaccharide (LPS)-stimulated NHBE cells and further evaluated its ability to decrease LPS-induced inflammation in the ferret airway.

Methods: NHBE cells were grown at air-liquid interface (ALI) to ciliated differentiation. Baseline and endotoxin (LPS)-stimulated IL-8 secretion was measured by enzyme-linked immunosorbent assay at air and basal sides with and without dapsone. Western blotting was used to determine signaling pathways. In vivo, ferrets were exposed to intratracheal LPS over a period of 5 days. Once inflammation was established, oral or nebulized dapsone was administered for 5 days. Intraepithelial neutrophil accumulation was analyzed histologically, and mucociliary transport was measured on the excised trachea.

Results: Dapsone, 1 μg/mL, did not influence unstimulated (basal) IL-8 secretion. Apical LPS stimulation induced both apical and basolateral IL-8, but basolateral LPS increased only basolateral IL-8. Dapsone inhibited polarized IL-8 secretion from ALI-conditioned cells. Dapsone also decreased LPS-induced IL-8 mRNA level. LPS led to phosphorylation of extracellular signal-regulated kinase 1/2, but not p38 MAPK or c-Jun NH(2)-terminal kinase. LPS also induced NF-κB p65 phosphorylation, an effect that was inhibited by dapsone. Both oral and aerosol dapsone decreased LPS-induced intraepithelial neutrophil accumulation, but only treatment with aerosol dapsone restored mucociliary transport to normal.

Conclusions: Dapsone, given either systemically or as an aerosol, may be useful in treating neutrophilic airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aerosols
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Bronchi / cytology
  • Bronchi / drug effects*
  • Bronchi / metabolism
  • Bronchitis / chemically induced
  • Bronchitis / drug therapy*
  • Bronchitis / pathology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dapsone / administration & dosage
  • Dapsone / pharmacology*
  • Dapsone / therapeutic use*
  • Disease Models, Animal
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Ferrets
  • Humans
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Phosphorylation / drug effects
  • Transcription Factor RelA / metabolism
  • Treatment Outcome


  • Aerosols
  • Anti-Inflammatory Agents
  • Interleukin-8
  • Lipopolysaccharides
  • Transcription Factor RelA
  • Dapsone
  • Mitogen-Activated Protein Kinase Kinases