Hypothetical mechanisms of action of an H1-antihistamine in asthma.
Some recent clinical studies carried out with the potent H1-antihistamine cetirizine (CTZ) suggest that this drug could be useful for the treatment of mild to moderate asthma and even for the prevention of the disease. Besides a potent antagonism of H1-receptors at bronchial level, this drug was also shown to exert a large series of anti-inflammatory effects in in vitro, ex vivo and in vivo pharmacological models and also in clinical situations in atopic subjects. All the data collected up to now suggest the possible existence in the molecule of a central key mechanism of action on resident cells especially involved in cell trafficking and bronchial inflammation, i.e a down-regulating effect on the nuclear factorKappaB (NFkappaB). This hypothesis was tested on human endothelial cells and a human epithelial pulmonary cell line using different experimental methods. The results showed that CTZ down-regulates the TNF-alpha-induced hyperactivation of NFKappaB in these two different resident cells at physiological concentrations.
Rihoux
J P
JP
UCB SA, Chemin du Foriest B-1420 Braine-l'Alleud, Belgium.
Michel
L
L
Arnold
R
R
König
W
W
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D017332:Cetirizine / Q000494:pharmacology* / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D016328:NF-kappa B / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D006634:Histamine H1 Antagonists; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017332:Cetirizine