Inhibition of histamine-induced human conjunctival epithelial cell responses by ocular allergy drugs

Objective: To evaluate the effects of topical ocular drugs with histamine H i-antagonist activity on histamine-stimulated phosphatidylinositol turnover and interleukin (IL) 6 and IL-8 secretion from human conjunctival epitheli al cells. Methods: Primary human conjunctival epithelial cell cultures were stimulate d with histamine in the presence or absence of test drugs. Phosphatidylinos itol turnover was quantified by ion exchange chromatography and cytokine co ntent of supernatants by enzyme-linked immunosorbent assay. Results: Antazoline hydrochloride, emedastine difumarate, levocabastine hyd rochloride, olopatadine hydrochloride, and pheniramine maleate attenuated h istamin-estimulated phosphatidylinositol turnover and IL-6 and IL-8 secreti on. Emedastine was the most potent in ligand binding, phosphatidylinositol turnover, and IL-6 secretion, with dissociation constant and 50% inhibitory concentrations of 1-3 nmol/L. Olopatadine, antazoline, and pheniramine exh ibited similar H-1-binding affinities (32-39 nmol/L). However, olopatadine was approximately 10-fold more potent as an inhibitor of cytokine secretion (50% inhibitory concentration, 1.7-5.5 nmol/L) than predicted from binding data, while antazoline and pheniramine were far less potent (20- to 140-fo ld) in functional assays. Levocabastine (dissociation constant, 52.6 nmol/L ) exhibited greater functional activity (50% inhibitory concentration, 8-25 nmol/L) than either antazoline or pheniramine. Conclusions: Histamine-stimulated phosphatidylinositol turnover and cytokin e secretion by human conjunctival epithelial cells are attenuated by compou nds with Hi-antagonist activity. However, antihistaminic potency alone does not predict anti-inflammatory potential. Olopatadine, emedastine, and levo cabastine were notably more potent than pheniramine and antazoline. Clinical Relevance: Selected topical ocular drugs with antihistaminic activ ity may offer therapeutic advantages to patients with allergic conjunctivit is by inhibiting proinflammatory cytokine secretion from human conjunctival epithelial cells.