Modulation of eosinophil survival by epinastine hydrochloride, an H1 receptor antagonist, in vitro.
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.
Watase
Fumitaka
F
Department of Otolaryngology, School of Medicine, Showa University, Tokyo, Japan.
Watanabe
So
S
Kanai
Ken-Ichi
K
Yamada
Naohiro
N
Sakaue
Satoshi
S
Asano
Kazuhito
K
Hisamitsu
Tadashi
T
Suzaki
Harumi
H
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
D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C053090:epinastine