Inhibition of Histamine-Induced Human Conjunctival Epithelial Cell Responses by Ocular Allergy Drugs

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Abstract
HUMAN CONJUNCTIVAL epithelial cells (HCEs) secrete cytokines after stimulation by various cell-activating agents. Gamache et al1 showed that primary cultures of HCEs secrete tumor necrosis factor α, interleukin (IL) 6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) after IL-1α, phorbol myristate acetate, and calcium ionophore A23187 treatment. The authors suggested that this capability of the conjunctival epithelium indicates a possible effector function for the tissue in allergic conjunctivitis. Other investigators have reported that histamine, a major mediator of allergic diseases, induces the production of cytokines by airway epithelium. For instance, GM-CSF release from human tracheal epithelial cells was significantly enhanced by exposure to 1-µmol/L histamine.2 In addition, histamine caused a dose-dependent stimulation of IL-6, IL-8, and GM-CSF release by normal and transformed human bronchial epithelial cells that appeared to occur via histamine H1-receptor activation.3 The proinflammatory properties of these cytokines are well documented. Elevated IL-6 levels have been reported to be associated with a variety of inflammatory conditions, including asthma, psoriasis, uveitis, and allergic rhinitis.4-7 Intravitreal injection of IL-6 has been shown to produce uveitis in rats and rabbits.8 Interleukin 8 is a potent member of the C-X-C family of chemokines. It promotes integrin expression, neutrophil degranulation, and chemotaxis of basophils and eosinophils.9-13

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