Histamine-Stimulated Cytokine Secretion from Human Conjunctival Epithelial Cells: Inhibition by the Histamine H1 Antagonist Emedastine

Abstract

The present studies demonstrate that histamine induces the secretion of IL-6, IL-8 and GM-CSF from human conjunctival epithelial cells in a dose- and time-dependent manner. The histamine antagonists emedastine (H₁), ranitidine (H₂) and thioperamide (H₃) were evaluated for their ability to inhibit secretion of these cytokines. Emedastine potently inhibited histamine-induced IL-6, IL-8 and GM-CSF secretion with mean IC₅₀ values of 2.23, 3.42 and 1.50 nM, respectively. Ranitidine and thioperamide failed to inhibit cytokine secretion over a wide dose range. These data suggest that mast cell derived histamine may stimulate inflammatory cytokine production in allergic conjunctivitis via activation of epithelial cell H₁ receptors. The histamine H₁ antagonist emedastine potently inhibits this response.