Modulation of eosinophil survival by epinastine hydrochloride, an H1 receptor antagonist, in vitro

In Vivo. 2008 Nov-Dec;22(6):687-91.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Culture Techniques
  • Cell Survival / drug effects*
  • Dibenzazepines / pharmacology*
  • Eosinophils / cytology*
  • Eosinophils / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Histamine H1 Antagonists / pharmacology*
  • Humans
  • Imidazoles / pharmacology*
  • Male
  • Middle Aged
  • Nasal Mucosa / cytology
  • Nasal Mucosa / pathology
  • Nasal Polyps / pathology
  • Nasal Polyps / surgery
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Dibenzazepines
  • Histamine H1 Antagonists
  • Imidazoles
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • epinastine