Histamine-stimulated cytokine secretion from human conjunctival epithelial cells: inhibition by the histamine H1 antagonist emedastine.
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.
Weimer
L K
LK
Ophthalmology Research, Alcon Laboratories, Fort Worth, Tex 76134, USA.
Gamache
D A
DA
Yanni
J M
JM
D001562:Benzimidazoles / Q000494:pharmacology*; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism
D001562:Benzimidazoles; D016207:Cytokines; D006634:Histamine H1 Antagonists; D015850:Interleukin-6; D016209:Interleukin-8; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C043345:emedastine