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Thomas R Vollmer, Megan E Cavet, Karen L Harrington, Stepan M Volhejn, Mary Richardson; Anti-inflammatory effects of the glucocorticoid loteprednol etabonate in human ocular and inflammatory cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6297.
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© ARVO (1962-2015); The Authors (2016-present)
Loteprednol etabonate (LE) is an ocular glucocorticoid (GC) which is rapidly metabolized to inactive metabolites in the ocular tissue, thus reducing the potential for side-effects observed with other topical GCs. The aim of this study was to compare the anti-inflammatory effects of LE with other GCs in human ocular and inflammatory cell types.
Human corneal epithelial cells (HCEpiC) and conjunctival fibroblasts (HConF) were challenged with IL-1β and human monocytes (THP-1) were challenged with LPS. Luminex technology was used to determine the effects of LE (0.1 - 1000 nM) on IL-1beta- or LPS-induced multiple cytokine release into the conditioned medium. The effect of LE (3 - 1000 nM) on IL-1beta-induced prostaglandin E2 (PGE2) release and cyclooxygenase-2 (COX-2) expression was also assessed in HConF, by ELISA and western blotting respectively. Dose response curves and IC50 values were generated. Dexamethasone (DEX) and prednisolone acetate (PA) were used as the controls. Fluorometholone (FM) and triamcinolone acetonide (TA) were also tested in HCEpiC.
IL-1beta or LPS induced measurable cytokine release in the three cell types studied, (GM-CSF, IL-6, IL-8 and MCP-1 in HCEpiC; G-CSF, IL-6, IL-8 and MCP-1 in HConF; and G-CSF, IL-1beta, IL-6, IL-8, IL-12p40, IP-10, MCP-1, MIP-1α, MIP-1beta and TNF-α in THP-1). LE significantly reduced LPS- or IL-1beta-induced cytokine release in a dose-dependent manner for measured cytokines, except MIP-1beta or TNF-α in THP-1. LE demonstrated comparable efficacy and potency to that of DEX in all cell types and also FM and TA in HCEpiC. In HConF, LE significantly inhibited PGE2 release to a similar extent as DEX, through a reduction in COX-2. The calculated LE IC50 values for cytokines and PGE2 were all below 10 nM in the different cell types. Prednisolone acetate was less potent and efficacious in reducing IL-1β- or LPS-induced cytokine and PGE2 release in each cell type.
LE acts as a potent and efficacious anti-inflammatory agent in human ocular and inflammatory cell types.
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