HISTAMINE-STIMULATED CYTOKINE SECRETION FROM HUMAN CONJUNCTIVAL EPITHELIAL-CELLS - INHIBITION BY THE HISTAMINE H-1 ANTAGONIST EMEDASTINE

The present studies demonstrate that histamine induces the secretion o f IL-6, IL-8 and GM-CSF from human conjunctival epithelial cells in a dose- and time-dependent manner. The histamine antagonists emedastine (H-1), ranitidine (H-2) and thioperamide (H-3) were evaluated for thei r 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 t hioperamide failed to inhibit cytokine secretion over a wide dose rang e. These data suggest that mast cell derived histamine may stimulate i nflammatory cytokine production in allergic conjunctivitis via activat ion of epithelial cell H-1 receptors. The histamine H-1 antagonist eme dastine potently inhibits this response.