title: Modulation of eosinophil survival by epinastine hydrochloride, an H1 receptor antagonist, in vitro.
abstract: The influence of epinastine hydrochloride (EP) on eosinophil survival was examined by an in vitro cell culture technique. Nasal epithelial cells (NECs) were stimulated with 25 ng/ml TNF-alpha in the presence of EP (10 to 30 ng/ml). After 24 h, the culture supernatants were obtained and used as conditioned media of NECs (CM). Eosinophils (1 x 10(3) cells/ml) prepared from healthy human peripheral blood were incubated with 25% CM and eosinophil survival was assessed by trypan blue dye exclusion test 48 h later. CM prepared from NEC cultures pre-treated with TNF-alpha and EP caused a decrease in eosinophil survival as compared with that from NEC cells pre-treated with TNF-alpha alone. The minimum concentration of EP that caused a significant decrease in eosinophil survival was 25 ng/ml. The addition of EP into eosinophil cultures did not cause inhibition of eosinophil survival, which was prolonged by stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF), even when 40 ng/ml EP was added to cell cultures. We then examined the levels of GM-CSF in CM by ELISA. Treatment of NECs with EP at more than 25 ng/ml, reduced the ability of NECs to produce GM-CSF in response to TNF-alpha stimulation. These results may suggest that EP suppresses eosinophil survival through the suppression of GM-CSF production from NECs induced by inflammatory stimulation and that this suppressive effect contributes, in part, to the therapeutic mode of action of EP on allergic diseases.
authors.affiliation: Department of Otolaryngology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Watase
authors.forename: So
authors.initials: S
authors.lastname: Watanabe
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kanai
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakaue
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Asano
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hisamitsu
authors.forename: Harumi
authors.initials: H
authors.lastname: Suzaki
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects*; D003984:Dibenzazepines / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000473:pathology; D009298:Nasal Polyps / Q000473:pathology / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C053090:epinastine