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

Background Cetirizine, a H-1-receptor antagonist, exerts besides its well-k nown anti-allergic potential an array of anti-inflammatory activities. In p articular 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 int erleukin-8 (IL-8) from human epithelial cells activated with agonists disti nct from histamine. Methods We used the human lung epithelial cell line A549 for our in vitro s tudies. IL-8 release was determined by IL-8 enzyme immunoassay, the intrace llular staining for IL-8 and NF-kB was analysed by FACS analysis and IL-8 m RNA steady state level was studied by Northern blot analysis. Confluent epi thelial cell monolayer were pre-incubated with cetirizine (0.01 -1.0 mu mol /L) for 30 min and afterwards activated with pro-inflammatory cytokines (TN F-alpha IL-1 beta, IL-6, IFN-gamma) or different agonists (PMA, NaF, respir atory syncytial virus [RSV]) for 24 h. Results Epithelial cells stimulated with TNF-alpha IL-1 beta, PMA and RSV, respectively, showed a significantly increased release of IL-8. Pre-incubat ion with cetirizine diminished the IL-8 release from cells activated with T NF-alpha or PMA in a significant manner. The reduced IL-8 release coincided with a diminished percentage of cells expressing IL-8. Northern blot analy sis revealed a reduced steady state level of IL-8 mRNA in cells pretreated with cetirizine and stimulated with TNF-alpha. Furthermore, a decreased amo unt of accessible DNA-binding sites of the nuclear factor kappa B (NF-kB) w as 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 lowe ring IL-8 gene expression. Therefore, cetirizine might exert anti-inflammat ory effects beyond its H-1-receptor antagonistic activity in the course of inflammatory respiratory tract disorders such as bronchial asthma and aller gic rhinitis.