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

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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.