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A. Pauly, C. Blondin, L. Riancho, C. Baudouin; Inhibition of Histamine–Induced Human Conjunctival Cell Release of Pro–inflammatory Cytokines IL–6 and IL–8 . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4843.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To investigate the effects of several H(1) receptor antagonists on histamine–induced release of inflammatory cytokines from human conjunctival epithelial cells. Methods:Conjunctival Wong–Kilbourne cells were cultured overnight in 6–well plates until 95% confluent. The following day, cells were stimulated for 30 minutes with anti–H(1) molecules prior to 24 hour–stimulation with histamine (30 µM). Supernatants were harvested and the production of IL–6 and IL–8 was quantified by enzyme–linked immunosorbent assay. Azelastine, ketotifen and levocabastine were tested at the following concentrations: 1 µM, 0.1 µM, 10 nM and 1 nM. Results:Human conjunctival epithelial cells had a low basal expression of both IL–6 and IL–8 cytokines. Histamine increased the release of IL–6 and IL–8 in cell supernatants and all the H(1) receptor antagonists tested presented dose–dependent inhibitory effects on IL–8 production. Azelastine, ketotifen and levocabastine were found to inhibit the release of IL–6 from histamine–induced conjunctival cells in a dose–dependent manner. Conclusions:This study confirms that histamine has pro–inflammatory effects on human conjunctival epithelial cells and that these cells may contribute to ocular inflammatory responses in allergic diseases. The ability of topical ocular anti–H(1) drugs to significantly reduce the production of IL–6 and IL–8 argues that these molecules may be useful tools in the treatment of inflammatory processes occurring in allergic ocular surface disorders.
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