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Clinical & Experimental Allergy

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

Authors

  • R. Arnold,

    1. Institute of Medical Microbiology and Immunology, AG Infektabwehr, Ruhr-University, Bochum, Germany,
    2. Institute of Medical Immunology, Charité-Campus Mitte, Humboldt University, Berlin, Germany,
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  • J.-P. Rihoux,

    1. Union Chimique Belge, Brussels, Belgium,
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  • W. König

    1. Institute of Medical Microbiology and Immunology, AG Infektabwehr, Ruhr-University, Bochum, Germany,
    2. Institute of Medical Microbiology, Otto-von-Guericke University, Magdeburg, Germany
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W. König Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Inst, für Medizinische Mikrobiologie, Leibziger Strasse 44, D-39120 Magdeburg, Germany.

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 μmol/L) for 30 min and afterwards activated with pro-inflammatory cytokines (TNF-α IL-1β, IL-6, IFN-γ) or different agonists (PMA, NaF, respiratory syncytial virus [RSV]) for 24 h.

Results

Epithelial cells stimulated with TNF-α IL-1β, 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-α 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-α. 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-α, 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.

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