Cetirizine counter-regulates interleukin-8 release from human epithelial cells (A549)

Clin Exp Allergy. 1999 Dec;29(12):1681-91. doi: 10.1046/j.1365-2222.1999.00630.x.

Abstract

Background: Cetirizine, a H1-receptor antagonist, exerts besides its well-known anti-allergic potential an array of anti-inflammatory activities. In particular epithelial cells activated in the presence of cetirizine showed a reduced ICAM-1 cell surface expression and a diminished release of sICAM-1.

Objective: We wondered whether cetirizine might influence the release of interleukin-8 (IL-8) from human epithelial cells activated with agonists distinct from histamine.

Methods: We used the human lung epithelial cell line A549 for our in vitro studies. IL-8 release was determined by IL-8 enzyme immunoassay, the intracellular staining for IL-8 and NF-kB was analysed by FACS analysis and IL-8 mRNA steady state level was studied by Northern blot analysis. Confluent epithelial cell monolayer were pre-incubated with cetirizine (0.01 -1.0 micromol/L) for 30 min and afterwards activated with pro-inflammatory cytokines (TNF-alpha IL-1beta, IL-6, IFN-gamma) or different agonists (PMA, NaF, respiratory syncytial virus [RSV]) for 24 h.

Results: Epithelial cells stimulated with TNF-alpha IL-1beta, PMA and RSV, respectively, showed a significantly increased release of IL-8. Pre-incubation with cetirizine diminished the IL-8 release from cells activated with TNF-alpha or PMA in a significant manner. The reduced IL-8 release coincided with a diminished percentage of cells expressing IL-8. Northern blot analysis revealed a reduced steady state level of IL-8 mRNA in cells pretreated with cetirizine and stimulated with TNF-alpha. Furthermore, a decreased amount of accessible DNA-binding sites of the nuclear factor kappa B (NF-kB) was determined by FACS analysis.

Conclusions: These results suggest that cetirizine reduced the release of IL-8 from A549 cells stimulated with PMA and TNF-alpha, respectively, by lowering IL-8 gene expression. Therefore, cetirizine might exert anti-inflammatory effects beyond its H1-receptor antagonistic activity in the course of inflammatory respiratory tract disorders such as bronchial asthma and allergic rhinitis.

MeSH terms

  • Blotting, Northern
  • Cetirizine / pharmacology*
  • Cytokines / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / immunology
  • Flow Cytometry
  • Histamine H1 Antagonists / pharmacology*
  • Humans
  • Interleukin-8 / metabolism*
  • Lung / cytology
  • Lung / immunology*
  • Respiratory Syncytial Viruses / immunology
  • Sodium Fluoride / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • Histamine H1 Antagonists
  • Interleukin-8
  • Sodium Fluoride
  • Tetradecanoylphorbol Acetate
  • Cetirizine