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Inhibitory effects of ketotifen on eotaxin‐dependent activation of eosinophils: consequences for allergic eye diseases
Author(s) -
Woerly G.,
Loiseau S.,
Loyens M.,
Schoch C.,
Capron M.
Publication year - 2003
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1034/j.1398-9995.2003.00081.x
Subject(s) - ketotifen , eotaxin , chemotaxis , allergic inflammation , eosinophil , immunology , eosinophil cationic protein , chemistry , immunoglobulin e , chemokine , pharmacology , inflammation , biology , biochemistry , antibody , receptor , asthma
Background: The aim of this study was to investigate the effects of ketotifen on different parameters of human eosinophil functions, namely chemotaxis, oxidative metabolism and mediator release, induced after activation. Methods: Eosinophils from hypereosinophilic patients or normal donors were purified by Percoll gradient and the magnetic cell separation system. Chemotaxis was studied using the Boyden chamber technique using three potent chemoattractants: formyl‐methionine‐leucine‐phenylalanine (fMLP), interleukin (IL)‐5 and eotaxin. Oxidative metabolism was determined by a luminol‐dependent chemiluminescence assay after activation with eotaxin or secretory immunoglobulin A (sIgA). The release of eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN) was measured by radioimmunoassay after activation with sIgA. Results: At pharmacologically active concentrations and in a dose‐dependent manner, ketotifen significantly inhibited the chemotaxis of eosinophils to fMLP, IL‐5 and eotaxin. The production of reactive oxygen species induced by eotaxin and sIgA was decreased by ketotifen, showing a more pronounced effect when cells were activated by eotaxin. Activation by sIgA resulted in ECP and EDN release, which was partially inhibited by ketotifen. Conclusions: Through inhibition of chemotaxis, ketotifen might limit the number of eosinophils at the inflammation site during allergic reaction. Furthermore, inhibition by ketotifen of main inflammatory mediators release suggests a potential role of the drug in limiting the pathological potential of eosinophils.